bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the GABA Receptor Agonist Muscimol on the Turnover of Brain Dopamine and on the Motor Activity of Rats
Authors: Andén Nils‐Erik , Grabowska‐Andén Maria , Wachtel Helmut
Published: July 2010

AbstractMuscimol (3‐hydroxy‐5‐aminomethylisoxazole) at a high dose (10 mg/kg intraperitoneally) elevated the concentration of brain dopamine in rats, decreased the utilization of dopamine and increased the synthesis of dopamine. The utilization of noradrenaline was accelerated rather than retarded by muscimol. Local application of muscimol to the nucleus accumbens of rats inhibited the motor activity in a dose‐dependent manner with only a slight subsequent hyperactivity. The effects are similar to those produced by GABA and they support the view that muscimol is a GABA receptor agonist.
Inhibition of ATP‐Induced Contraction in the Guinea‐pig Urinary Bladderin Vitroandin Vivo
Authors: Sjögren C. , Andersson K.‐E.
Published: July 2010

AbstractContractions were elicited by adenosine 5′‐triphosphate (ATP) in the guinea‐pig urinary bladderin vitroandin vivo. In isolated detrusor strips, tetrodotoxin (3.1 × 10‐6‐4.4 × 10‐5M) did not affect contractions induced by a submaximum concentration (10‐3M) of ATP, nor did atropine (1.7 × 10‐6‐ 2.1 × 10‐4M), or the anticholinergic agent PR 197 within the concentration range 2.6 × 10‐8‐ 2.6 × 10‐5M. In higher concentrations (5.2 × 10‐5‐2.6 × 10‐4M), PR 197 inhibited the ATP‐response by 60‐70% in a way that was not clearly concentration‐related. Isoprenaline (10‐7‐2.0 × 10‐5M) and noradrenaline (2.5 × 10‐6‐10‐4M) reduced the ATP‐induced contractions by up to 79%. The effects of the amines were abolished by propranolol (5.2 × 10‐6‐3.8 × 10‐5M). Adenosine, 1.0‐2.0 × 10‐2M, reduced the ATP‐response by about 50%; in lower concentrations, it had no effect. Nifedipine, 7.8 × 10‐7‐1.2 × 10‐5M, reduced the responses by 15‐795%. Indomethacin (≤2.0 × 10‐4M), and theophylline (2.0 × 10‐4M) had no consistent effects on ATP‐induced contractions. Exposure of the preparations to a calcium‐free medium reduced and abolished the ATP‐response within 60 min. Intravenous injection of ATP (1 ‐20 mg/kg) caused a rapid and transient increase in intravesical pressure in the anaesthetized guinea‐pig. The effect of ATP (3mg/kg) was reduced by atropine(5‐10 mg/kg) by approximately 35%. PR 197 (2.5‐5 mg/kg) abolished the ATP‐response. Isoprenaline (5‐100 pg/kg) caused a 53‐95% inhibition that could be blocked by propranolol (1 mg/kg). The inhibiting effect of noradrenaline (10‐100,μg/kg) could not be blocked by propranolol (1 mg/kg). Adenosine (1.5‐3.0 mg/kg) given immediately before ATP completely inhibited the ATP‐response. Nifedipine, 0.1‐0.2 mg/kg, reduced the ATP‐induced contraction by 34 to 100%. It is concluded that the ATP‐induced contraction is elicited by a direct effect on the smooth muscle cell. It can be inhibited non‐specifically by drugs with different modes of action.
The Effect of Prolonged Pentobarbital Anaesthesia on Cardiac Electrophysiology and Inotropy of the Dog Heartin Situ
Authors: Amlie Jan P. , Owren Torbjörn
Published: July 2010

AbstractThe effect of prolonged pentobarbital anaesthesia was tested on the dog heartin situby means of His bundle electrography and programmed electrical stimulation, monophasic action potential recordings from the right ventricle and measurements of peak dp/dt obtained by Millar tip transducer in the left ventricle. Sixteen dogs were used. Immediately after catheterization during anaesthesia, a slight decreased heart rate, a reduction in the conduction velocity and an increase in the functional refractory period of the atrioventricular node occurred. From 15 to 30 min. after catheterization we observed no change in cardiac electrophysiology during the 8 hrs observation period. A slight decrease in contractility, however, appeared towards the end of the period. We conclude that dogs anaesthetized with pentobarbital could serve as a suitable model for testing drug effect on cardiac electrophysiology and contractility. The limitations of the model area are discussed.
The Determination of Naproxen by Spectrofluorometry and its Binding to Serum Proteins
Authors: Mortensen A. , Jensen E. Bjern , Petersen P. Bernth , Husted S. , Andreasen F.
Published: July 2010

AbstractA fluorometric method for the determination of naproxen in serum, albumin solutions and protein free buffer solutions is described. The detection limit is about 10 ng/ml. Furosemide, thiopental and salicylic acid did not show any disturbing fluorescence while phenprocoumon did. Thein vitrobinding of naproxen in albumin solutions and serum was studied by equilibrium dialysis. A small but significant increase was found in the percentual binding in albumin solutions as compared to serum. The percentual binding was not affected by changes in the pH from 5‐8. By fitting the binding data to a model assuming two classes of binding sites, association constants and binding capacities were determined. A very high affinity and a high capacity were found. The association constant for the first class of binding sites was higher for human serum albumin than for Serum (8.5 versus 5.3 · 106M‐1). The difference in the protein binding to the first class of binding sites in human serum albumin and serum can be explained by the existence of a competitive inhibitor in serum.
Paroxetine: Pharmacokinetics, Tolerance and Depletion of Blood 5‐HT in Man
Authors: Lund J. , Lomholt B. , Fabricius J. , Christensen J. A. , Bechgaard E.
Published: July 2010

Abstract The tolerance of paroxetine (FG 7051). as well as its pharmacokinetics and reduction of 5‐HT in blood, has been investigated in man. Three normal, healthy volunteers were administered the single doses 10, 25. 50, and 75 mg orally, and three volunteers received 10. 25, and 50 mg per day for seven or fourteen days. No toxic effect on blood. kidney, liver. heart or general condition was found by chemical and physical examinations. The pharmacokinetic studies revealed a dose dependent systemic availability, a rather slow elimination (tl,2 = approximately 16 hrs), a good fit to a one compartment open model, and an almost complete metabolism of the substance. 25 mg paroxetine per day gave a maximal reduction of 5‐HT in the blood within 2‐3 weeks (to approximately 0.03 pg/nil). The 5‐HT levels returned to the basic levels during a three to four weeks drug‐free period.
Supersensitivity of the Rat Urinary Bladder Following »Chemical Sympathectomy«
Authors: Ekström Jörgen
Published: July 2010

Abstract6‐hydroxydopamine (100 mg/kg injected intravenously twice with a weekly interval) was used for the destruction of the adrenergic nerves in the rat detrusor muscle. Two to three weeks after the first injection of this substance the sensitivity of the detrusor muscle to parasympathomimetic and sympathomimetic drugs was tested by recording the intravesical pressurein situ.The sensitivity to methacholine was found to be unchanged, whereas a supersensitivity to noradrenaline, adrenaline, phenylephrine and isoprenaline was found to have developed, thus involving both α‐adrenoceptor mediated contraction and β‐adrenoceptor mediated relaxation. The supersensitivity was of the postjunctional type.
Effect of Toxogonin and P2S on the Toxicity of Carbamates and Organophosphorus Compounds
Authors: Sterri Sigrun H. , Rognerud Bjarne , Fiskum Stein E. , Lyngaas Synneve
Published: July 2010

AbstractToxogonin (80 mg/kg intraperitoneally) given 15 min. prior to the administration of organophosphorus insecticides dimethoate, malathion, parathion and azinphos‐methyl, organophosphorus warfare agents soman and tabun, or carbamates physostigmine, pyridostigmine and aldicarb, reduced the toxicity in mice of these agents by increasing their LD50 dose 1.5‐3 fold. The toxicity of the carbamate insecticide carbaryl, however, was significantly increased by toxogonin. Similar results were obtained for P2S (150 mg/kg intraperitoneally) with respect to the toxicity of dimethoate, soman and pyridostigmine, whereas no effect could be detected on the toxicity of tabun. Only a slight reduction in the toxicity of physostigmine was observed. The acetylcholinesterase activity in erythrocytes, cerebrum and diaphragm of surviving mice 20 hours after organophosphate intoxication was similar both in toxogonin and P2S treated animals and untreated animals.
Effects of Digoxin on Isolated Human Pulmonary Vessels
Authors: Mikkelsen E.
Published: July 2010

AbstractIn isolated human pulmonary arteries and veins the contractile response to noradrenaline (1.8×10‐5M) was 33±7.4% and 20±4.5% (Mean±S. E.M.) of that induced by potassium (127 mM). A variable degree of spontaneous contractile activity was recorded in the vein preparations. This activity was abolished by nifedipine (2.9 × 10‐6M). Digoxin (10‐6M) induced contractions in pulmonary vessels. In the arteries, the digoxin contraction developed slowly and reached a maximum amplitude of 90±4% (Mean±S.E.M.)of the potassium evoked contraction. In the veins, the amplitude of the digoxin contraction was 32±5% of that induced by potassium. Digoxin (10‐6M) also increased the maximum response to noradrenaline and potassium in both arteries and veins. In the arteries, the noradrenaline and potassium contractions increased to 211±6.8% and 145±8.9 of control, and in the veins to 169 ± 13.5% and 163 ± 9.9%, respectively. Nifedipine in concentrations which completely relaxed arterial and venous preparations contracted by potassium, had only a slight relaxing effect on digoxin induced contraction. It is concluded that digoxin increases the tension in pulmonary arteries and veins, and increases the maximum response to noradrenaline and potassium in both types of vessels. The digoxin induced contraction is highly resistant to blockade of extracellular calcium influx.
A New Anti‐inflammatory Derivative of Imidazole which is Less Ulcerogenic than Indomethacin in Rats
Authors: Corell Tim , Jensen Karen Meller , Splawinski Jacek
Published: July 2010

AbstractThe mechanism of the anti‐inflammatory activity and ulcerogenicity of (2‐dimethylamino‐1(2)‐methyl) ethyl ester of the 1‐(2‐carboxyethyl)‐2‐(p‐chlorophenyl)‐4,5‐bis‐(p‐methoxyphenyl)‐imidazole (A‐162‐ester) was compared with that of indomethacin in rats and enzymatic preparations derived from other species. A‐162‐ester was found to be deesterified in plasma to A‐162. A‐162‐ester was about 3 times less anti‐inflammatory and about 17 times less ulcerogenic than indomethacin. A‐162‐ester, when given orally, decreased prostaglandin I2(PGI2) biosynthesis by gastric mucosa. The IC50 was close to the ulcerogenic ED50. Indomethacin ‐ in the same test ‐ was 37 times more potent than A‐162‐ester and the PGI2inhibition and ulcerogenic dose‐response curves for indomethacin were parallel. In otherin vitrosystems of prostaglandin (PG) biosynthesis, the inhibitory activity of A‐162 was comparable to that of indomethacin. It is concluded that the ulcerogenicity of indomethacin results from a high affinity of this drug to gastric mucosal wall PG‐synthetase which leads to decreased PGI2formation at this site. The relatively low ulcerogenicity of A‐162‐ester most probable results from a lower affinity of this drug to the same site.
Effects of Digoxin on Isolated Human Peripheral Arteries and Veins
Authors: Mikkelsen E. , Andersson K.‐E. , Pedersen O. Lederballe
Published: July 2010

AbstractIn isolated human crural arteries and veins, digoxin induced slowly developing, long‐lasting contractions. These contractions were not diminished by α‐adrenoceptor blockade or by washing, but were abolished by the calcium antagonist nifedipine. In the presence of digoxin, the maximum contractile responses to noradrenaline (18 μM) and potassium (127 mM) markedly increased, and the glycoside shifted the noradrenaline concentration‐response curve to the left. Immersion of vein preparations in calcium‐free medium for 30 min. abolished the digoxin contraction, whereas responses could still be elicited by potassium and noradrenaline. A change of the extracellular potassium concentration from 4.6 mM in normal Krebs to 1.15 mM always increased tension in vein preparations, whereas a change from 4.6 to 6.9 and 9.2 mM caused relaxation, and a further increase to 13.8 mM contracted the preparations. After pretreatment with digoxin (1μM), a potassium change from 4.6 to 1.15 mM caused relaxation and all concentrations exceeding 4.6 mM produced contraction. It is concluded that digoxin has a direct contractile effect on isolated human crural vessels, and that this effect is dependent on the extracellular calcium concentration. In the presence of the glycoside, the responses to noradrenaline and potassium are potentiated. Vascular responses to changes in extracellular potassium concentration are influenced by digoxin.
In VivoAbsorption of Phenytoin from Rat Small Intestine and its Inhibition by Phlorizin
Authors: Johansson Ö. , Lindberg T. , Melander A.
Published: July 2010

AbstractIn vivoabsorption of phenytoin from the small intestine was studied by anin vivoclosed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 μmol/1 was administered in dissolved form. Polythylene glycol 4000 was used as a non‐absorbable marker. The concentrations of phenytoin in the intestinal lumen. in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 percent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/1 and 1 mmol/1 phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 μmol/1) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 μmol/1. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the rat.
Effects of a Sugar Mixture on Blood Alcohol Parameters and Impairment in the Intact Rat
Authors: Jones A. W. , Goldberg L. , Neri A.
Published: July 2010

AbstractThe effects of a sugar mixture containing 43% glucose and 36% fructose on ethanol metabolism and on ethanol‐induced impairment were studied in intact rats. When ethanol was given orally mixed with the sugars there was a significant reduction in the area of the blood alcohol time curve accompanied by a decrease in the peak ethanol concentration and a slowing in the rate of ethanol absorption. The whole curve followed a lower course and the time for complete removal of ethanol from the body was markedly reduced even though the slope of the elimination phase (β) was not significantly increased. Ethanol‐induced impairment as measured using a tilting plane device was significantly less when ethanol was given mixed with the sugars and paralleled the reduced area and duration of the blood alcohol curve. The magnitude of the effect observed on blood alcohol levels and impairment was dependent on the dose of sugars administered in relation to the alcohol dose. When the sugars were given orally after absorption and distribution of ethanol were complete the slope of the elimination phase (β) was increased by 30%. These findings point to an increased rate of ethanol metabolism in rats in the presence of sugars. The action of the sugars prevails only for the first few hours after administration thereafter the rate of ethanol metabolism returns to normal.
The Role of Ethyl and Fluorine Substitution in the 4′‐Position for N,N‐Diethyl‐4‐aminoazobenzene Mutagenicity and Azo Reduction
Authors: Søderlund Erik J. , Dybing Erik , Nordenson Svein , Tjelta Egil
Published: July 2010

Abstract:The mutagenicity and azo reduction rate of N,N‐diethyl‐4‐aminoazobenzene (DEAB) were influenced by substitution in the 4′‐position with a ethyl or a fluorine group. The parent dye (DEAB) was shown to be slightly mutagenic withSalmonella typhimuriumTA98 using Aroclor 1254‐pretreated 9000 x g supernatant fractions from rat liver. Introduction of a 4′‐ethyl group in DEAB did not affect mutagenicity of the dye, but a 4‐fluoro group markedly enchanced its mutagenicity. DEAB underwent azo reduction and its reduction rate was influenced by 4′‐substituents. A 4′‐fluoro group in DEAB increased its azo reduction rate, while a 4′‐ethyl group abolished it. Inhibitors of cytochrome P‐450 also inhibited 4′‐fluoro‐DEAB mutagenicity and azo reduction.
Prostaglandins and the Cardiotoxic Effects of Doxepin in Rabbits and Guinea‐pigs
Authors: Puisto E.‐L. , Mattila M. J. , Elonen E. , Eränkö P.
Published: July 2010

Abstract:Intravenous administration of tricyclic antidepressants to rabbits leads to dysrhythmias largely attributable to their non‐specific membrane effects. Further experiments with doxepin (Dx) were conducted to assess an eventual contribution by prostaglandins (PG) to these events. Dx infused intravenously to conscious or anaesthetized guinea‐pigs proved as cardiotoxic as amitriptyline hut more toxic than protriptyline, thus confirming our previous results in rabbits. PG F2α given intravenously before or during the Dx infusion failed to antagonize cardiotoxicity. In conscious rabbits, pretreatment with drugs (aminophenazon, indomethacin, tolfenamic acid) known to inhibit PG synthesis failed to modify the Dx cardiotoxicity asalsodid PG F2α which elevated blood pressure, however. PG F2α also failed to counteract the ouabain cardiotoxicity in anaesthetized guinea‐pigs and major Ba++‐induced dysrhythmias in conscious rabbits. Our results suggest that a) at least Dx induced dysrhythmias are unresponsive to PGs, and that b) previous speculations about PGsas antiarrhythmic agents may be exaggerated.
Myocardial Pharmacokinetics and Pharmacodynamics of Dipyridamole in the Isolated Rabbit Heart
Authors: Nielsen‐Kudsk F. , Askholt J.
Published: July 2010

Abstract:The myocardial accumulation and disposition pharmacokinetics of the antithrombotic drug dipyridamole were investigated in isolated perfused and spontaneously beating rabbit hearts. The rabbit myocardium behaved pharmacokinetically as a two‐compartment system with regard to the drug. The half‐lives of the α‐phase of distribution and of the β‐phase of disposition were about 1.4 and 6.3 min., respectively. Perfusion with a modified Krebs‐Henseleit solution containing 5.1 μg ml−1of dipyridamole caused an accumulation of about 140 ug g−1of myocardial tissue at steady state. The initial measured pharmacokinetic parameters were unchanged after perfusion with the drug for 60 min. The accumulating dipyridamole in the rabbit heart caused a progressive decrease in myocardial contractility to about 65 %. This was accompanied by a decrease in the ratio of contraction rate to oxygen consumption to about 0.7 as an expression of reduced myocardial efficiency. The coronary flow rate was not significantly increased. The heart beating frequency decreased only slightly and no dromotropic effects were observed.
Effect of cGMP Derivatives on Contraction Relaxation Cycle, Release of Norepinephrine and Protein Kinase Activity in Guinea Pig Vas Deferens
Authors: Axelsson Krister L. , Andersson Rolf G. G. , Wikberg Jarl E. S.
Published: July 2010

Abstract:Contractions of the guinea pigs vas deferens were induced by field stimulation and the effects of derivatives of cGMP were tested on the contraction‐relaxation cycle. Relaxation was induced by 8‐Br‐cGMP and O2′‐mb‐cCMP. On the contrary, db‐cGMP and N2‐mb‐cGMP potentiated the contraction. The relaxant effect of 8‐Br‐cGMPwas not mimiced by 8‐Br‐5′GMP, instead the latter caused the opposite effect. Since neither 8‐Br‐cGMP nor db‐cGMP affected the release of norepinephrine on field stimulation the cGMP derivatives induced their effects at a postsynaptic site. 8‐Br‐cGMP was found to be 100‐fold more potent than cGMP to stimulate protein kinase activity in crude extracts from guinea pig was deferens. N2‐mb‐cGMP and O2′‐mbcGMP were approximately equipotent to cGMP while db‐cGMP was less active. 8‐Br‐5′‐GMP did not stimulate the protein kinase. It is suggested that the results support the hypothesis that cGMP acts as a relaxant in the smooth muscle of the vas deferens. The potentiation caused by db‐cGMP and N2‐mb‐cGMP on contractions could be dependent on the substitution in the guanine moiety of the molecules with the butyryl group. Their effect was thus probably unrelated to a specific cGMP effect.
Effect of Age and Route of Administration on LD50 of Lithium Chloride in the Rat *
Authors: Petersen Kurt Pfeiffer
Published: July 2010

Abstract:Male inbred rats were used to determine the lethal dose of lithium chloride. The rats were 3 weeks, 6 weeks, 3 months and 6 months old, and lithium chloride was given intraperitoneally, subcutaneously and orally. In relation to age, LD50 was significantly higher in rats of 6 weeks after oral administration than LD50 in rats of 3 and 6 months. No differences were found following intraperitoneal and subcutaneous administration. In relation to route of administration, LD50 was significantly higher in rats of 3 and 6 weeks after oral administration than LD50 after intraperitoneal and subcutaneous administration. This difference was not found in rats of 3 and 6 months. It is concluded that age and route of administration are of significance for LD50 of lithium chloride in the rat.
Cardiac Lesions in the Frog Induced by Adrenaline
Authors: Carlsten A. , Poupa O. , Winell S.
Published: July 2010

Abstract:Adrenaline (A) causes gross lesions of the ventricular wall in frogs living both at 12° and 25°. At 12° the sensitivity of the heart to A is higher than at 25°. Single or multiple ventricular aneurysm, provoked by A could not be prevented by propranolol. The resistance of the myocardium towards cyanide anoxia is lowered after A especially at 25°. In preliminary experiments with noradrenaline the same cardiotoxic effects are observed.
Nature of Lowered 5‐Hydroxytryptamine Uptake by Blood Platelets of Patients with Down's Syndrome
Authors: Tukiainen Erkki , Tuomisto Jouko , Westermarck Tuomas , Kupiainen Heli
Published: July 2010

Abstract: Disturbance of central serotoninergic system has been suggested in Down's syndrome (DS). In this syndrome the 5‐HT concentration in blood platelets is below normal, but the mechanism behind this has been controversial. Recently. evidence has accumulated indicating a decreased active transport of 5‐HT possibly due to lowered activity of Mg++‐dependent Na+‐K+ ‐stimulated adenosine triphosphatase. In the present study the kinetic analysis of 5‐HT uptake by blood platelets from DS patients revealed a decreased Vmax suggesting decreased transport function but an unchanged affinity to the uptake receptors, as indicated by normal Km values. The controls were mentally retarded patients from the same institute. The uptake continued in a linear fashion up to 20 min., suggesting an unchanged storage of 5‐HT. Also the effect of zinc on the 5‐HT uptake was studied; plasma zinc levels have been noted to be lowered in DS infants. In vitro zinc caused a dose‐dependent inhibition ofuptake at 10−4 an M. In vivo. after 2 weeks treatment 135 mg/day orally no significant effect was noted.
Contralateral Circling Behaviour Induced by Intranigral Injection of Morphine and Enkephalin Analogue FK 33–824 in Rats
Authors: Kaakkola Seppo
Published: July 2010

Abstract:Contralateral circling behaviour induced by intranigral injection of morphine or an enkephalin analogue, FK 33–824, was studied in rats. Both morphine(0.625–10.0μg)and FK 33–824(1.25–40.0 ng) evoked the same kind of contralateral circling behaviour when injected into the substantia nigra. FK 33–824 was about 1000 times more potent than morphine and its effect lasted a little longer. Pretreatment with naloxone (5 mg/kg subcutaneously or 1 μg intranigrally) almost completely blocked the circling induced by intranigral morphine or FK 33–824. The lesion of the ipsilateral nigrostriatal dopaminergic pathway with 6‐hydroxydopamine significantly antagonized both morphine‐ and FK 33–824‐induced circling. Pretreatment with d‐amphetamine (l mg/kg intraperitoneally) significantly increased the intensity of the circling induced by morphine or FK 33–824, and pretreatment with haloperidol (0.5 mg/kg subcutaneously) attenuated this intensity. Pretreatment with pilocarpine (10 mg/kg intraperitoneally) or mecamylamine (2 mg/kg intraperitoneally) inhibited the circling, whereas pretreatment with atropine (10 mg/kg intraperitoneally) or nicotine (0.2 mg/kg subcutaneously) increased morphine‐ and FK 33–824‐induced circling. Pretreatment with muscimol (0.5 mg/kg subcutaneously) did not significantly increase morphine‐induced circling but tended to increase FK 33–824‐induced circling. Pretreatment with bicuculline (3 mg/kg intraperitoneally) slightly but significantly inhibited both morphine‐ and FK 33–824‐induced circling. Pretreatment with strychnine (0.25 mg/kg intraperitoneally) did not modify the circling induced by morphine or FK 33–824. The results show that the contralateral circling behaviour induced by intranigral injection of morphine and FK 33–824 seems to be mediated by the activation of the dopaminergic nigrostriatal system.
Mechanisms of the responses to Non‐Cholinergic, Non‐Adrenergic Nerve Stimulation and to ATP in Isolated Rabbit Urinary Bladder: Evidence for ADP Evoked Prostaglandin Release
Authors: Husted Steen , Sjögren Christer , Andersson Karl‐Erik
Published: July 2010

Abstract:The contractile effects of ATP and related purine compounds on the isolated rabbit detrusor were investigated. It was found that ATP produced an initial rapid, phasic contraction followed by a slowly developing and maintained increase in tension. ADP caused a contraction closely mimicking the tonic response to ATP. The ADP induced contraction and the tonic response to ATP could both be abolished by indomethacin. β, γ‐methylene ATP (APPCP), which is not degraded to ADP, elicited a rapid, phasic response, which could be abolished by nifedipine. AMP, dibutyryl‐cAMP, and adenosine in low concentrations had no contractile effects; high concentrations of adenosine and 2‐chloroadenosine, which is resistant to adenosine deaminase, decreased tone and spontaneous activity. The amplitude of the ATP induced contraction was positively correlated to the Ca2+‐concentration in the extracellular medium; removal of Ca2+abolished the ATP contraction before the responses to high K+and carbachol disappeared. Responses to electrical field stimulation, mediated by non‐cholinergic, non‐adrenergic mechanisms were abolished by nifedipine and significantly reduced by indomethacin. It is concluded that in isolated rabbit detrusor, a direct contractile response can be elicited only by tripolyphosphates (ATP and APPCP), and that the diphosphate moiety ADP stimulates synthesis of prostaglandins. The similarity between the effects of stimulation of non‐cholinergic, non‐adrenergic neurones and the phasic response to ATP supports the view that in rabbit detrusor ATP may be involved in excitation.
Does Cellular Tolerance Develop to the Lethal Effect of Ethanol in the Rat?
Authors: Hillbom M. E. , Pösö A. R.
Published: July 2010

Abstract:Rats were kept intoxicated by forced intragastric administration of a liquid diet containing ethanol for 4 days or 3 weeks. Control animals were pair‐fed with the same liquid diet containing starch instead of ethanol. After withdrawal the animals pretreated for 3 weeks showed tolerance to the lethal effect of ethanol as indicated by significantly prolonged survival and higher cerebrospinal fluid ethanol level at death after an oral test dose of 15 g/kg. The tolerance disappeared within a week. Metabolic tolerance, although present, did not prolong the survival of the animals, and the results suggest involvement of cellular tolerance in the central nervous system.
The Effect of Propranolol on the Electroencephalogram in Normal and Ethanol Dependent Rats
Authors: Hemmingsen R. , Holm‐Jensen J. , Trojaborg W.
Published: July 2010

Abstract:Electroencephalograms were recorded from scalp electrodes placed over the cerebral hemispheres of rats withdrawing from ethanol. The purpose was to investigate whether administration of the β‐adrenergic receptor blocker propranolol changed the EEG during that condition. The animals were artificially ventilated with an air mixture of 70% N2O:30% O2and PaO2PaCO2and mean arterial blood pressure were kept constant. There were no significant differences in EEG frequencies or amplitudes between abstinent animals and controls neither before nor 20 min. after intravenous administration of propranolol 2 mg/kg body weight. Similarly, there was no EEG changes during 3 min. of photic stimulation. It has been reported that electrophysiological abnormalities during physical ethanol dependence are generated in subcortical brain structures but the 4 day intoxication period used in the present study seems too short to involve the cerebral cortex.
The Effect of Single Dose Ergotamine Tartrate on Peripheral Arteries in Migraine Patients: Methodological Aspects and Time Effect Curve
Authors: Tfelt‐Hansen Peer , Eickhoff Jens H. , Olesen Jes
Published: July 2010

Abstract: Ergotamine tartrate (0.5 mg/70 kg) was given intravenously to 17 migraine patients. Arm, finger, ankle and big toe systolic blood pressures were measured with strain gauge technique for up to 4 hours and again after 22 hours. Systolic arm blood pressure increased transiently (duration less than 3 hours). Peripheral systolic blood pressures decreased in all patients (for toes a few to 55 mmHg) and at 22 hours well sustained decreases were still found. Further 10 migraine patients received 2–4 mg ergotamine tartrate as suppositories and peripheral systolic blood pressures were measured for 3 days. A decrease in peripheral systolic blood pressure was found after 24 hours but had disappeared after 48 hours. Contrary to common belief the present study investigating the effect of ergotamine directly on arteries has shown a long duration of its vasoconstrictory effect. Thus the effect of a single dose of ergotamine on the arteries should be followed for days.
Toxicity and Pharmacological Properties of Surface‐active Alkyltrimethylammonium Bromides in the Rat
Authors: Isomaa Boris , Bjondahl Kaj
Published: July 2010

Abstract:Acute intravenous toxicity and pharmacological properties of surface‐active alkyltrimethylammonium bromides (C10‐C20) were studied in female rats. The acute toxicity of the surfactants decreased with an increasing length of the alkyl chain up to a chain length of 16 carbon atoms. Death appeared to be due to respiratory failure. The twitch responses of sciatic nerve‐gastrocnemius muscle preparations were reversibly depressed at direct and indirect stimulation following intravenous injections of sublethal doses of C10‐C14. Doses blocking the twitch responses of indirectly stimulated gastrocnemius corresponded to about half the LD50, and at these doses C10‐C14caused a transient decrease in respiratory rate. The C16homologue caused respiratory arrest without affecting the twitch responses of gastrocnemius at relative low intravenous doses. Sublethal intravenous doses of C12‐C20caused, apparently due to vasodilatation, a tarnsient fall in arterial blood pressure. The depressor response increased and the twitch response decreased with an increase in the length of the alkyl chain up to a chain length of 16 carbon atoms. Both the depression of skeletal muscle contraction and the vasodilatation is suggested to originate from a non‐specific effect of the surfactants on muscle cells.
Metabolism of Lidocaine in Human Liver in Vitro
Authors: Hermansson Jørgen , Glaumann Hans , Karlén Bo , von Bahr Christer
Published: July 2010

Abstract: We have incubated the local anaesthetic drug lidocaine with microsomes from human adult livers. The metabolites deethylated lidocaine (MEGX) and aromatically hydroxylated lidocaine (3‐hydroxylidocaine) were isolated by high performance liquid chromatography and quantitated by the liquid scintillation counting technique. The deethylation rate markedly exceeded the hydroxylation rate also at very low lidocaine concentrations. This pattern differs from that detected earlier with rat liver microsomes where aromatic hydroxylation is significant at low lidocaine concentrations, but it is similar to that in female guinea pig microsomes. These findings show the importance of performing this type of experiments also with human materials.
Studies on the Interaction and Distribution of Selenite, Mercuric, Methoxyethyl Mercuric and Methyl Mercuric Chloride in Rats. I. Analysis of Brain, Liver, Kidney and Faeces
Authors: Mengel Helle , Karlog Ole
Published: July 2010

Abstract The interaction of selenium with methyl mercury, methoxyethyl mercury and mercuric chloride was studied in a 37 days' experiment with rats. Liver, kidney, brain and faeces were analysed for mercury and selenium at the end of the experimental period. Selenium supplementation increased the retention of mercury in liver, when mercuric chloride was given, in liver and brain when methyl mercury was given, and in all tissues examined when methoxyethyl mercury was given. The Hg/Se molar ratios in the tissues have been calculated and are found to vary considerably.
Enhancement of Hepatic Drug Biotransformation by a Short‐term Intermittent Turpentine Exposure in the Rat
Authors: Järvisalo J. , Vainio H.
Published: July 2010

AbstractAn inhalation exposure of male rats to 300 p.p.m. of a commercial turpentine 6 hrs daily 5 days a week for 8 weeks enhanced the activities of drug biotransformation enzymes of liver microsomes considerably. The activities of NADPH cytochromecreductase and 7‐ethoxycoumarin deethylase, and microsomal content of cytochrome P‐450 were increased 35–60 % during the first weeks of the experiment, but had a tendency to return towards the control values later on. A similar enhancement of activities was also found in liver microsomal epoxide hydratase and UDPglucuronosyltransferase, but these enzyme activities tended to adapt less during the experiment. The turpentine treatment increased the affinity of liver microsomal cytochrome P‐450 to α‐pinene (the main component of the turpentine). The present data suggests that exposure to turpentine is able to modify considerably the biotransformation of drugs.
Differences in the Response of Hepatic and Intestinal Drug Metabolizing Enzymes in Rats Following Carbon Tetrachloride and/or Phenobarbital Treatment
Authors: Koivusaari Ulla , Lang Matti , Hietanen Eino
Published: July 2010

AbstractThe activities of the microsomal drug metabolizing enzymes in the liver and intestinal mucosa of rats were studied after the intraperitoneal administration of carbon tetrachloride and/or subcutaneous phenobarbital administration. The membrane phospholipid content was decreased after carbon tetrachloride treatment indicating destruction in the membrane structure. Aryl hydrocarbon hydroxylase activity was decreased in the liver and intestinal mucosa after treatment with CCl4alone and in combination with phenobarbital. The CCl4treatment increased the intestinal epoxide hydratase activity but decreased the activity in the liver. The hepatic UDPglucuronosyltransferase was slightly induced by phenobarbital and the activity was elevated by the CCl4treatment. In the intestinal mucosa the enhanced UDPglucuronosyltransferase activity was observed only after phenobarbital pretreatment and the activity was decreased by CCl4. These results support the view that epoxide hydratase and UDPglucuronosyltransferase enzymes occupy different locations in the endosplasmic reticulum of intestinal mucosa than of liver.
Urinary and Biliary Metabolites of Phenanthrene in the Coalfish (Pollachius virens)
Authors: Solbakken Jan Erik , Palmork Karsten H. , Neppelberg Tore , Scheline Ronald R.
Published: July 2010

AbstractMetabolites present in the urine and bile of coalfish(Pollachius virens) 48 hrs after the intragastric administration of phenanthrene (75 mg/kg) were studied. Using gas chromatographic‐mass spectrometric methods small amounts of unchanged compound, all five of the possible monohydroxy derivatives and the 1,2‐and 9,10‐dihydrodiols of phenanthrene were identified in these samples. The major metabolite detected was phenanthrene‐1,2‐dihydrodiol which was excreted mainly as glucuronide and/or sulfate conjugates.
The Adrenoceptor Blocking Properties of the New β2‐Selective Antagonist, IPS 339 on Tracheal Smooth Muscle and on Slow Contracting Skeletal Muscle
Authors: Holmberg Eva , Jeppsson Ann‐Britt , Lamm Carl Johan , Waldeck Bertil
Published: July 2010

AbstractThe β‐adrenoceptor blocking properties of IPS 339 and propranolol were studied on isolated preparations of trachea and of the slow‐contracting soleus muscle from the guinea‐pig. Both compounds antagonized the relaxation of the trachea and the depression of subtetanic contractions of the soleus produced by the β2‐selective agonist, terbutaline. On the soleus muscle the pA2‐values for IPS 339 and propranolol were similar and close to those obtained for propranolol on the trachea. However, on the trachea the slope of the Schildplot for IPS 339 against terbutaline became less than one and a reliable pA2‐value could not be calculated.
Renal Response to Potassium Infusion in Rats given Lithium for Prolonged Time
Authors: Olesen Ole Vendelin , Thomsen Klaus
Published: July 2010

AbstractThe effects of infusion of potassium chloride was studied in Wistar rats given lithium by the food for more than 3 weeks. The animals were anaesthetized with amytal and three clearance periods were run. During periods 1 and 3 0.15 M NaCl was infused at a rate of 0.02 ml/min. for 60 min. and in period 2 0.5 M KCl was infused at the same rate for 90 min. Potassium infusion led to an increase of potassium excretion. Sodium excretion and urine flow were positive linear correlated to the potassium excretion but in rats given lithium the effect of potassium on sodium excretion was about eight times higher and the effect on urine flow about thirteen times higher than the effects on control rats not given lithium. The concentration of Na and K in the urine of the lithium‐treated group were within a narrow range and almost unaffected by potassium infusion. Lithium clearance and the fractional excretion of lithium rose significantly during potassium infusion. Inulin clearance was almost unaffected by the potassium infusion. The results indicate that potassium infusion in rats given lithium for prolonged time leads to an increase of renal sodium, water and lithium excretion.
Tetrahydro‐β‐carbolines and Corresponding Tryptamines:In VitroInhibition of Serotonin and Dopamine Uptake by Human Blood Platelets
Authors: Airaksinen Mauno M. , Svensk Heikki , Tuomisto Jouko , Komulainen Hannu
Published: July 2010

AbstractTetrahydro‐β‐carbolines (THBCs), 6‐methoxyharmalan and norharman and the corresponding open chain tryptamines studied inhibited 5‐hydroxytryptamine (5‐HT) and dopamine (DA) uptake in human blood platelets. 1‐methyl‐THBCs were better inhibitors of DA than 5‐HT uptake but THBCs generally were far more potent inhibitors of 5‐HT uptake than of DA uptake. 6‐methoxy‐1,2,3,4‐tetrahydro‐β‐carboline was as potent as 5‐HT itself in3H‐5‐HT uptake inhibition in platelets and the inhibition was competitive. All the β‐carbolines studied were more potent inhibitors of3H‐DA uptake than DA itself. Contrary to results in rat brain synaptosomes, THBCs were more potent in platelets than the corresponding tryptamines with the freely rotating ethylamine side chain. Unsaturated β‐carbolines were weaker inhibitors than THBCs. The clear difference in the rank order of potencies of these compounds in human platelets and rat brain synaptosomes demonstrates that these different model systems for amine uptake studies do not always give comparable results. The results also suggest that there are differences in the uptake systems for 5‐HT and DA in human platelets.
Effect of Atropine and Methylatropine on Human Vaginal Blood Flow, Sexual Arousal and Climax
Authors: Wagner Gorm , Levin Roy J.
Published: July 2010

AbstractNo experimental data on the regulatory mechanism of the change in vaginal blood flow occuring at sexual arousal exist. Six women Were in a controlled laboratory study given atropine 0.035 mg/kg intravenously. The basal vaginal blood flow was recorded by a heat probe kept at set temperature on the vaginal wall. During sexual stimulation the flow was increased as in women when no drugs are applied and orgasm was unaffected as well. The neurotransmitter has been supposed to be acetylcholine but the present experiments suggest that it is not an atropine sensitive traditional muscarinic transmission. Methylatropine was given in five subjects and neither in these cases any effect on the vaginal vascular response was observed.
Intestinal Metabolism of DNOC and DNBP in the Rat
Authors: Ingebrigtsen Kristian , Frøslie Arne
Published: July 2010

AbstractThe metabolism of the dinitrophenols DNOC and DNBP and their respective monoamino derivatives, 6‐ANOC and 6‐ANBP, was studied in rat caecal incubates. All of the compounds were reduced to their corresponding diamino metabolites. The results are discussed in relation to the comparative toxicology of the dinitrophenols with special regard to a possible significance of the intestinal metabolites.
Dissociation by Lithium of Hormone‐induced Formation of Cyclic AMP and Release of Glycerol in Isolated Rat Fat Cells
Authors: Thams Peter , Geisler Arne
Published: July 2010

AbstractIt has been suggested that lithium exerts some of its pharmacological actions by inhibition of the membrane‐bound enzyme adenylate cyclase. However, the relationship between the lithium inhibition of adenylate cyclase and the corresponding physiological parameters, e.g. lipolysis, has not been investigated. In the present study it was found that lithium inhibited both the norepinephrine‐induced accumulation of cAMP and release of glycerol in isolated rat fat cells, but only in the lower dose range of norepinephrine. At maximally effective concentrations of norepinephrine, where in the presence of 40 mM of lithium the formation of cAMP was reduced by approximally 40%, lipolysis remained unaffected. The basal content of cAMP and the basal release of glycerol were not inhibited by lithium. In addition to the inhibitory effect of lithium, lithium was found to stimulate the release of glycerol. This stimulatory effect of lithium may be explained by a prevention by lithium of the feedback inhibition by free fatty acids of adenylate cyclase and/or triglyceride lipase, since it could be avoided by increasing the concentration of bovine serum albumin in the incubation medium. It is concluded that lithium by inhibition of hormone‐stimulated adenylate cyclase activity inhibits lipolysis only at submaximal hormone concentrations. This dissociation by lithium of cAMP accumulation and glycerol release may suggest that at least at high concentrations of norepinephrine cAMP‐independent factors are involved in lipolysis.
Disposition Pharmacokinetics of Lorazepam in the Rabbit
Authors: Nielsen‐Kudsk F. , Jakobsen P.
Published: July 2010

AbstractThe disposition pharmacokinetics of the sedative and anxiolytic drug lorazepam were investigated in 8 rabbits in relation to intravenous bolus injection of 0.3 or 0.6 mg of the compound. Lorazepam showed distinct linear two‐compartment characteristics with a mean biological half‐life (t1/2β) of only 73.7 min. ±17.3 S.D. The mean half‐life of the α‐phase of distribution was 18.4 min. ±4.7 S.D. The mean apparent steady state volume of distribution was 1.64 1 kg‐1±0.27 S.D., Vc‐mean was 1.11 1 kg‐1± 0.24 S.D. and Vdarca2.261kg‐1± 0.16 S.D. The calculated apparent volume of the peripheral compartment amounted to 0.53 1 kg‐1±0.28 S.D. Compared to human data the distribution of lorazepam takes place somewhat slower in an about two‐times as great apparent volume of distribution, while the disposition of the compound proceeds with an about 20 times as high rate.
Calcium antagonistic effects of terodiline in rabbit aorta and human uterus
Authors: Østergaard J. R. , Østergaard K. , Andersson K.‐E. , Sommer L.
Published: July 2010

AbstractThe possible calcium antagonistic action of the anti‐anginal drug terodiline was investigated by two experimental techniques. In isolated preparations of rabbit aorta and pregnant human uterus exposed to a calcium‐free medium and then depolarized by potassium, terodiline in concentrations of 4.5–36 μM inhibited contractions produced by cumulative addition of calcium to the extracellular medium. This effect of terodiline could be reversed by high concentrations of calcium. Within the same concentration range, terodiline also reduced potassium‐induced45Ca influx in isolated aorta without affecting calcium efflux. It is suggested that terodiline, which structurally has similarities to prenylamine and fendiline, like these drugs can be classified as a calcium antagonist.
Anticholinergic and calcium antagonistic effects of terodiline in rabbit urinary bladder
Authors: Husted S. , Andersson K.‐E. , Sommer L. , Østergaard J. R.
Published: July 2010

AbstractThe effects of terodiline on contractions induced in isolated rabbit detrusor by carbachol and potassium, and by electrical field stimulation were investigated. Terodiline relaxed preparations contracted by carbachol and potassium and, when added 15 min before stimulation, decreased the contractile responses to these agents in a concentration‐dependent way. Terodiline more effectively inhibited carbachol than potassium induced contractions. The “pure” calcium antagonist nifedipine had the opposite effect. Both atropine and terodiline caused a parallell shift to the right of the concentration‐response curve to carbachol. The maximum contractile tension and slope were not affected, suggesting a competitive antimuscarinic effect within the concentration range used. Atropine was approximately 750 times more potent than terodiline. The maximum inhibitory effect of atropine and the calcium antagonist nimodipine on the electrically induced response were 40 % and 69 %, respectively. Terodiline caused complete inhibition of the response, as also did a combination of nimodipine and atropine. — The results suggest that terodiline in low concentrations has mainly an antimuscarinic action. To this, a calcium antagonistic effect is added at higher concentrations. The two‐fold action of the drug makes it an effective inhibitor of bladder contraction, and an interesting tool for investigations of bladder contractility.
Terodiline inhibition of human bladder contraction. Effects in vitro and in women with unstable bladder
Authors: Rud T. , Andersson K.‐E. , Boye N. , Ulmsten U.
Published: July 2010

AbstractTerodiline, a drug with anticholinergic and calcium antagonistic properties, effectively relaxed carbachol‐contracted, isolated human bladder preparations. In the concentrations used, terodiline displaced to the right the concentration‐response curve obtained on cumulative addition of carbachol. The maximum response was slightly reduced only at the highest terodiline concentration used (5μM), suggesting a mainly competitive antimuscarinic effect. Nine patients, aged 12–78 years, suffering from urge urinary incontinence were investigated by simultaneous urethro‐cystometry before and after treatment with terodiline 12.5 mg twice or three times daily for 10 days. The patients reported subjective improvement with almost no side effects. Objectively, the number of uninhibited bladder contractions and the amplitude of the contractions decreased. The bladder capacity was almost doubled. There were no marked effects on bladder and urethral pressures at rest, and only two of the investigated patients had slight residual urine after treatment.

The results suggest that terodiline is a promising alternative to existing drugs for inhibition of undesired detrusor activity.