bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECT OF SOME TRICYCLIC AND NONTRICYCLIC ANTIDEPRESSANTS ON [3H]IMIPRAMINE BINDING AND SEROTONIN UPTAKE IN RAT CEREBRAL CORTEX AFTER PROLONGED TREATMENT
Authors: BRUNELLO N. , RIVA M. , VOLTERRA A. , RACAGNI G. 
Published: August 2009

Summary—Chronic administration of different antidepressant drugs reduced the number of [3H]imipramine ([3H]IMI) binding sites in rat cerebral cortex. In the same experimental conditions, fluvoxamine and dothiepin, as well as desmethylimipramine, induced an increase in the maximal velocity of high affinity serotonin (5HT) uptake in cortical slices, whereas citalopram and viloxazine were ineffective in this regard.Our results indicate that even if 5HT uptake and [3H]IMI binding sites are located on the same nerve terminals, they are differently modulated. Increased Vmaxof the 5HT uptake process could be due to a rebound phenomenon after withdrawal from drugs that acutely inhibit 5HT uptake. The effect on [3H]IMI sites might be explained through either the agonist properties of the drugs towards these sites or the involvement of mechanisms still unknown.
ROLE OF EXTRACELLULAR CALCIUM IN THE EFFECTS OF SUBSTANCE P AND NEUROKININ A ON GUINEA PIG TRACHEA AND HUMAN BRONCHUS
Authors: MATRAN R. , NALINE E. , ADVENIER C. , LOCKHART A. , TRICOT J.F. , REGOLI D. 
Published: August 2009

Summary—Whether the influux of calcium through voltage‐operated channels is involved in the stimulatory effects of substance P and neurokinin A in aiways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium‐free Krebs solution and tested with inhibitors of calcium channels.In calcium‐free Krebs solution, the myotropic effects of substance P (10−7M), neurokinin A (3.10−8M), acetylcholine (2.10−5M), and histamine (2.10−5M) were reduced by 27–57%, while those of potassium chloride and tetraethylammonium were practically abolished.Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10−8‐10−6M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10−5‐10−4M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine.In neither preparation did the calcium agonist Bay K 8644 (10−6M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage‐operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.
CALCIUM ANTAGONISTS, A NEW CLASS OF ANTIHYPERTENSIVE AGENTS*
Authors: SCHWARTZ J. 
Published: August 2009

Summary—The mechanism of action of Ca++antagonists remains debatable. Not all voltage‐sensitive calcium channels have the same sensitivity to organic calcium blockers. Those in smooth muscle are clearly more sensitive than those in heart, and at least some of those in brain are not blocked at all. It is possible that in vascular smooth muscle, calcium antagonists act essentially on receptor‐operated channels.In any case, calcium antagonists are potent antihypertensive agents, but in clinical practice they have limitations. A second generation of dihydropyridines may provide a higher degree of therapeutic selectivity.
5‐HYDROXYTRYPTAMINE STIMULATES TWO DISTINCT ADENYLATE CYCLASE ACTIVITIES IN RAT BRAIN: HIGH‐AFFINITY ACTIVATION IS RELATED TO A 5‐HT1SUBTYPE DIFFERENT FROM 5‐HT1A, 5‐HT1B, AND 5‐HT1C
Authors: FAYOLLE C. , FILLION M.‐P. , BARONE P. , OUDAR P. , ROUSSELLE J.‐C. , FILLION G. 
Published: August 2009

Summary—5‐HT binding sites of the 5‐HT1type are heterogeneous and appear to comprise several subtypes (5‐HT1A, 5‐HT1Band 5‐HT1C); their physiological role is as yet unclear. The stimulation of adenylate cyclase induced by 5‐HT has been investigated in membrane fractions prepared from rat brain cortex.Enzymatic activity was determined by measuring cAMP production with an HPLC technique. It was shown that 5‐HT stimulates adenylate cyclase activity with 2 activation constants (Kact): one shows a high apparent affinity (Kact= 0.8 nM) and the other a lower apparent affinity (Kact= 0.30 μM). The latter activity, induced by micromolar concentrations of 5‐HT, was inhibited by spiperone at concentrations that block 5‐HT1Abinding. 5‐Methoxytryptamine, bufotenin, and LSD also had a stimulatory biphasic effect on adenylate cyclase activity, whereas trifluoromethylphenylpiperazine, 5‐carboxyamidotryptamine, 8‐hydroxy‐(2‐di‐n‐propylamino)tetralin, RU 24969 had a monophasic effect. Enzyme activation by drugs acting in the micromolar range was inhibited by spiperone (1 μM), suggesting a link between this activation and 5‐HT1Asites.On the other hand, the high‐affinity activation of the enzyme induced by 5‐HT, 5‐methoxytryptamine, bufotenin, LSD, and the activation induced by TFMPP were not inhibited by spiperone (1 μM), by propranolol (3 μM), or by mesulergine (0.1 μM), which selectively block 5‐HT1A, 5‐HT1B, and 5‐HT1Csites. Inhibition was produced by dihydroergotamine, methysergide, cinanserin, and mianserin, but not by naloxone, phenoxybenzamine, and phentolamine. Therefore, these activations seem related to 5‐HT1receptors but not to 5‐HT1A, 5‐HT1B, or 5‐HT1Csites.Accordingly, binding of [3H]5‐HT to 5‐HT1‐like sites was examined in the presence of spiperone (1 μM) and propranolol (3 μM); in these conditions, a high‐affinity site (KD= 3.4 nM) was indeed revealed. The relative potencies of a series of drugs that stimulate or inhibit the activation of the adenylate cyclase with a high affinity and their ability to inhibit this binding of [3H]5‐HT showed a positive correlation, strongly suggesting a direct relation between this recognition site for 5‐HT and the production of a second messenger (cAMP). Moreover, this potential receptor is shown to be heterogeneously distributed within the brain, and was localized postsynaptically at serotonergic synapses.
DRUG PHARMACOKINETICS IN THE OBESE*
Authors: CHEYMOL G. 
Published: August 2009

Summary—In the obese, modifications in body constitution (higher percentage of fat and lower percentage of lean tissue and water) can affect drug distribution in the tissues. For slightly liposoluble molecules (e.g., digoxin, antipyrine), the equilibrium distribution volume (V), total and per kilogram weight, is significantly less than that of control subjects. With lipophilic drugs (e.g., barbiturates, benzodiazepines), this parameter is significantly increased, explaining the prolongation of the plasma elimination half‐life. For drugs that are almost equally soluble in water and oil (methyl xanthines, aminoglycosides), the V is slightly increased in the obese.The other main factors involved in drug diffusion in the tissues are binding to plasma and tissue proteins, and regional blood flow. In the obese the binding of drugs to albumin does not seem to be altered. A marked increase in plasma α‐glycoprotein acid and in propranolol binding has been reported in some studies; this has not been corroborated by other authors. Although the cardiac output and total blood volume are increased in the obese, the blood flow per gram of fat is less than in nonobese subjects. This could limit diffusion in the tissues of some lipophilic drugs. Studies on hepatic clearance of drugs are not available in the obese, but hepatic histological alterations have been described. In most publications concerning drugs with biotransformation as the principal elimination route, the total plasma clearance is not reduced. Up to the present, there are no reports of any impairment involving renal elimination of drugs in the obese.Dose‐adjustment of hydrophilic drugs is assessed according to the ideal weight of the individual obese subject; with lipophilic drugs the loading dose can be fixed according to the total weight; calculation of the maintenance dose depends on possible changes in the total clearance.
NEUROTRANSMITTERS AND INTRAOCULAR PRESSURE*
Authors: LAPALUS P. , ELENA P.P. 
Published: August 2009

Summary— The role of the ocular autonomic nervous system in IOP regulation has been well established. Pharmacological and autohistoradiographic studies confirmed the high density of beta2 and alpha2 receptors on ciliary processes and iris epithelium. Their respective pharmacological activation or blockade is discussed. The role of other ocular neurotransmitters is also complex, as shown by the paradoxical similar action of dopamine agonists and antagonists on IOP.Concerning the cholinergic system, ocular muscarinic receptors are pharmacologically not well documented. Numerous other neurotransmitters may modulate IOP without necessarily leading to the development of new drugs. Drugs of the future will probably concentrate on dopaminergic agonists, cAMP‐stimulators such as forskolin, prostaglandins, and cannabinoids.
RELAXATION OF RABBIT MIDDLE CEREBRAL ARTERIES IN VITRO BY H1 HISTAMINERGIC AGONISTS IS INHIBITED BY INDOMETHACIN AND TRANYLCYPROMINE
Authors: KIM L. EA , SERCOMBE R. , OUDART N. 
Published: August 2009

Summary— The H1‐histaminergic agonists 2‐pyridylethylamine (2‐PEA) and 2‐methylhistamine relaxed potassium‐constricted, perfused, rabbit middle cerebral arteries at low concentrations (3times10−11 to 3 times 10−8M) and constricted them at high concentrations (3 times 10−7 to 3 times 10−4M). The relaxation and the contraction were not antagonized by propranolol (up to 3times 10−6M) given 30 min before, suggesting that beta‐adrenergic mechanisms were not involved. When 2‐PEA was tested on arteries constricted with uridine triphosphate (UTP), similar results were obtained. In the UTP‐constricted arteries, the 2‐PEA‐induced responses were competitively antagonized by 3times 10−9M mepyramine. Together with previous work (Ea Kim et al., 1986), these results are compatible with the hypothesis that H1‐receptors were responsible for both the relaxation and the contraction observed.When either indomethacin (10−8, 3times 10−7, or 10−5M), dexamethasone (10−5M), or tranylcypromine (10−5 or 10−4M) were tested on the response to 2‐PEA or 2‐methylhistamine, these inhibitors suppressed the relaxation or reversed it to a contraction. Furthermore, they potentiated the contraction induced by these agonists. These results favour the hypothesis that the H1‐mediated relaxation in rabbit cerebral arteries may in part involve the release of prostaglandins, especially prostacyclin. The participation of such a prostanoid in histaminergic relaxation seems exclusively an H1‐mediated mechanism, since the relaxation induced by the H2‐agonist dimaprit (in the presence of mepyramine) was not antagonized by either indomethacin (3times 10−7M) or tranylcypromine (10−4M).
COMPARISON OF THROMBOLYTIC, FIBRINOLYTIC, AND FIBRINOGENOLYTIC PROPERTIES OF TISSUE PLASMINOGEN ACTIVATOR, STREPTOKINASE, SINGLE‐CHAIN UROKINASE, HIGH MOLECULAR WEIGHT AND LOW MOLECULAR WEIGHT UROKINASE IN HUMAN PLASMA IN VITRO
Authors: Samama M. , NGUYEN G. , DESNOYERS P. , LOURENCO D.M. , FRETAULT J. , HORELLOU M.H. , CONARD J. , SZWARCER E. , VERDY E. , VAHANIAN A. 
Published: August 2009

Summary— Thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator (t‐PA) from melanoma cells (mt‐PA), recombinant t‐PA (rt‐PA), streptokinase (SK), single‐chain urokinase plasminogen activator (scu‐PA), and high and low molecular weight urokinase (HMW UK, LMW UK) were compared in vitro by means of systems using human plasma.Thrombolytic activities were tested on standard or labeled hanging clots. When compared on the basis of urokinase international units, t‐PA appeared to be slightly more active than scu‐PA and streptokinase, and about 10‐fold more active than both preparations of UK when they were diluted in plasma.Fibrinolytic activity was evaluated by measuring the lysis time of recalcified plasma containing variable amounts of thrombolytic agents. t‐PA was shown to be twice as active as HMW UK, which was itself more active than LMW UK. When scu‐PA and both types of UK were compared on bovine fibrin plates, they showed similar fibrinolytic activity, but the t‐PA calibration curve was not parallel to those obtained with UK and scu‐PA.Relative thrombolytic and fibrinogenolytic properties were studied for each thrombolytic agent. For similar thrombolytic activities, fibrinogenolysis provoked by scu‐PA was less marked than with t‐PA and with both UK, while SK showed the highest activity. Our results demonstrate that the thrombolytic/fibrinogenolytic ratio is much more favorable to t‐PA and scu‐PA than to both forms of UK. Another observation clearly shows that fibrinogenolysis can be induced in vitro in human plasma by high doses of t‐PA. This consequence may be important since the therapeutic use of t‐PA can be associated with high concentrations of t‐PA, and thus t‐PA infusion could lead in vivo to severe fibrinogen breakdown. In addition, the methodology described could be useful in standardizing comparison between different species of thrombolytic agents.
RENAL EFFECTS OF NIFEDIPINE IN HEALTHY NORMOTENSIVE VOLUNTEERS. EFFECTS OF DOSE, FORMULATION, DURATION OF TREATMENT, AND CHLOROTHIAZIDE COADMINISTRATION
Authors: ADEBAYO G.I. , COKER H.A.B. , FAGBURE F. 
Published: August 2009

Summary—Renal effects of nifedipine were assessed in 3 groups of healthy normotensive volunteers. In the first group (N = 10), a single 20‐mg dose of the slow‐release formulation caused an increase in 8‐h sodium excretion (P<0.025) and urine volume (P<0.005). Natriuresis (P<0.05) and diuresis (P<0.05) were still evident after 1 wk of pretreatment, but were significantly attenuated (P<0.05), in each case, compared to levels after a single dose. Natriuresis and diuresis after 2 wk of intake were indistinguishable from control levels.In another group of 8, a single 10 mg dose of the conventional formulation (capsule) effected natriuresis (P<0.01) and diuresis (P<0.001) similar to those associated with intake of a single 20‐mg dose of the slow‐release formulation. Natriuresis and diuresis associated with a 20‐mg single dose of the conventional formulation were not different from control but were less than those following intake of the 10‐mg dose (P<0.025 in each case).In the third group of 6, nifedipine, though weaker than chlorothiazide, promoted natriuresis (P<0.025) and diuresis (P<0.025) of the thiazide without augmenting its kaliuresis. In all the groups, there were no changes in creatinine clearance, and nifedipine did not alter kaliuresis.It is suggested that natriuretic and diuretic effects of nifedipine in healthy normotensive individuals are dependent on the dose employed, the formulation used, and the duration of treatment. Moreover, although the effects of nifedipine and chlorothiazide are possibly additive, the calcium channel blocker is a weaker natriuretic and diuretic agent than the thiazide.
QUANTITATIVE ANALYSIS OF SERUM METHOHEXITAL BY GLC USING CAPILLARY COLUMN AND NITROGEN‐SELECTIVE DETECTION
Authors: LE NORMAND Y. , DE VILLEPOIX C. , ATHOUEL A. , KERGUERIS M.F. , BOURIN M. , LAROUSSE C. 
Published: August 2009

Summary— A gas chromatographic method for routine quantitation of methohexital in plasma samples is reported. One‐step extraction in organic phase, the use of a fused silica capillary column, and nitrogen‐selective detection permit simple, precise, and sensitive determination of methohexital in plasma. A linear relationship is described between peak height ratio and methohexital concentrations ranging from 0.125 to 50.0 μg/ml (r=0.998). The sensitivity limit of the assay was 6 ng/ml in plasma. No interfering peak was observed with numerous other drugs.The procedure was successfully applied to the determination of pharmacokinetic parameters of methohexital after IV administration or continuous infusion in a child and an adult.
ANTIHYPERTENSIVE DRUGS AND BARORECEPTOR REFLEX CONTROL OF HEART RATE AND BLOOD PRESSURE
Authors: BERDEAUX A. , GIUDICELLI J.F. 
Published: August 2009

Summary—The arterial baroreceptor reflex (BR; aortic and carotid sinus BR) and the cardiopulmonary BR are the most important reflexes acting as buffer systems for the maintenance of arterial pressure around a fixed physiologic value. They act as permanent inhibitory systems on the central cardiovascular structures and they can be either activated or deactivated by using selective techniques. During chronic hypertension there are structural alterations of the peripheral and/or central components of the BR that become «reset», with a shift in the function curve relating BR activity to blood pressure (BP) in the direction of higher pressure values. As a consequence of the hypertension‐induced resetting phenomenon, both the threshold pressure and sensitivity of BR are disturbed. However, if BR resetting during hypertension clearly decreases the sensitivity of BR control of heart rate (HR), BR control of peripheral resistance and arterial pressure as a whole is preserved and even increased when hypertension develops. Thus, this apparent discrepancy between BR control of HR and BP during hypertension demonstrates that evaluation of an antihypertensive therapy on reflex control of HR alone cannot predict what will happen to BR control of the whole cardiovascular system. Regarding BR control of HR, in contrast to the classical arteriolar vasodilators such as hydralazine and its derivatives, the majority of the modern antihypertensive drugs do not evoke reflex tachycardia in response to lowering of BP in normotensive or hypertensive subjects. Although the intrinsic pharmacologic mechanisms of action of these drugs on BR may be quite different (e.g., α,‐or β‐adrenoreceptor blocking agents, converting enzyme inhibitors, certain calcium‐channel blockers of the phenyldihydropyridine group, and so on), they all shift in a parallel manner the set‐point of the BR response curve towards lower pressures, with no change in HR or R‐R interval. Generally, this resetting phenomenon occurs after several weeks or months of antihypertensive therapy, but it can also occur acutely (e.g.after IV injection) after administration of drugs such as prazosin or ketanserin. Finally, antihypertensive agents such as clonidine and methyldopa can simultaneously reset the BR and increase its sensitivity, thus leading to almost complete restoration of control of HR response despite the concomitant decrease in BP.Regarding BR control of blood pressure, only captopril and especially celiprolol (a β1‐adrenoreceptor blocking drug with vasodilating properties) are able to restore almost normal BR control of arterial pressure.
CALCIUM ANTAGONISTS, A NEW CLASS OF ANTIHYPERTENSIVE AGENTS
Authors: SCHWARTZ J. 
Published: August 2009

Summary— The mechanism of action of Ca+ + antagonists remains debatable. Not all voltage‐sensitive calcium channels have the same sensitivity to organic calcium blockers. Those in smooth muscle are clearly more sensitive than those in heart, and at least some of those in brain are not blocked at all. It is possible that in vascular smooth muscle, calcium antagonists act essentially on receptor‐operated channels.In any case, calcium antagonists are potent antihypertensive agents, but in clinical practice they have limitations. A second generation of dihydropyridines may provide a higher degree of therapeutic selectivity.
DRUG PHARMACOKINETICS IN THE OBESE
Authors: CHEYMOL G. 
Published: August 2009

Summary—In the obese, modifications in body constitution (higher percentage of fat and lower percentage of lean tissue and water) can affect drug distribution in the tissues. For slightly liposoluble molecules (e.g., digoxin, antipyrine), the equilibrium distribution volume (V), total and per kilogram weight, is significantly less than that of control subjects. With lipophilic drugs (e.g., barbiturates, benzodiazepines), this parameter is significantly increased, explaining the prolongation of the plasma elimination half‐life. For drugs that are almost equally soluble in water and oil (methyl xanthines, aminoglycosides), the V is slightly increased in the obese.The other main factors involved in drug diffusion in the tissues are binding to plasma and tissue proteins, and regional blood flow. In the obese the binding of drugs to albumin does not seem to be altered. A marked increase in plasma α‐glycoprotein acid and in propranolol binding has been reported in some studies; this has not been corroborated by other authors. Although the cardiac output and total blood volume are increased in the obese, the blood flow per gram of fat is less than in nonobese subjects. This could limit diffusion in the tissues of some lipophilic drugs. Studies on hepatic clearance of drugs are not available in the obese, but hepatic histological alterations have been described. In most publications concerning drugs with biotransformation as the principal elimination route, the total plasma clearance is not reduced. Up to the present, there are no reports of any impairment involving renal elimination of drugs in the obese.Dose‐adjustment of hydrophilic drugs is assessed according to the ideal weight of the individual obese subject; with lipophilic drugs the loading dose can be fixed according to the total weight; calculation of the maintenance dose depends on possible changes in the total clearance.
COMPARATIVE HEMODYNAMIC STUDY OF A NEW AMINOSTEROID: LND‐623 WITH ITS 20α‐ISOMER: LND‐369, AND WITH DIGOXIN AND DIGOXIGENIN‐RHAMNOSIDE IN THE ANESTHETIZED DOG
Authors: WEISSENBURGER J. , HECKLE J. , BIOUR M. , POIRIER J.M. , JARREAU F.X. , JAILLON P. , CHEYMOL G. 
Published: August 2009

Summary—Hemodynamic effects of LND‐623, a new aminosteroid lacking the C17 lactone ring and the C14 hydroxyl group common to the natural glycosides, were studied in the pentobarbital‐anesthetized dog and compared to those of its 20α‐isomer LND‐369 and of digoxin and digoxigenin‐rhamnoside (DRh). Twenty‐four mongrel dogs were divided into 4 groups. Group I received either LND‐623 or saline on study day 1 and the other drug or saline 1 wk later. Saline was replaced by digoxin in group II, digoxigenin‐rhamnoside in group III, and LND‐369 in group IV. All drugs except LND‐369 were infused as 3.10−1mol.kg−1.min−1over 20 minutes. LND‐369 was infused at twice the dose.LND‐623 increased left ventricular dP/dt for at least 3 h with a peak at end‐infusion or 15 min later, accompanied by a transient vasopressor effect. LND‐369 induced, at twice the dose, an inotropic effect of comparable magnitude but of shorter duration. Inversely, it provoked a more marked and prolonged vasopressor effect than its 20β‐isomer, LND‐623. Maximal digoxin inotropic effect occurred later but was of comparable magnitude to that induced by LND‐623. Its vasopressor effects reached a plateau rapidly and remained sustained until min 200. Digoxigenin‐rhamnoside inotropic but not vasopressor effects are weaker than those of LND‐623.It is concluded that LND‐623, although lacking the most common structural features of the natural cardiac glycosides, provoked rapid and sustained inotropic activities with transient vasopressor effects. These time‐course effects differ from digoxin, and these differences are unrelated to their sugar‐moiety characteristics. LND‐623 inotropic effect is twice as potent as its 20α‐isomer.