bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of d‐amphetamine, Org 2766, scopolamine, and physostigmine on repeated acquisition of four‐response chains in rat
Authors: Howard James L. , Pollard Gerald T. 
Published: January 2005

AbstractAdult rats were trained to emit a different four‐response sequence on three levers for food reinforcement in each daily two‐hour session. Four sequences of putatively equal difficulty were used, with each sequence recurring every fourth session. Within‐session errors declined as a function of practice. Most subjects showed a significant idiosyncratic sequence bias. d‐amphetamine, tested at 0.1–2.0 mg/kg, increased errors as a function of dose. Org 2766 had no effect. Scopolamine and physostigmine, tested at 0.01–1.0 mg/kg, increased errors only at the highest doses, which produced tremor or ataxia. Results were generally consistent with previous results from other species. It was concluded that repeated acquisition in the rat is feasible for behavioral pharmacology and toxicology but that long training times and sequence bias limit its practicality.
The effects of lidocaine and hexamethonium on prostaglandin F2‐alpha‐ and histamine‐induced bronchoconstriction in sulfur dioxide‐treated beagle dogs
Authors: Malo P. E. , Griffin R. L. 
Published: January 2005

AbstractThe effects of local deposition of the topical anesthetic lidocaine and of ganglionic blockade by hexamethonium were investigated in pharmacologic bronchoconstriction with sulfer dioxide (SO2)‐induced hyperreactive beagle dogs. Control bronchopulmonary provocations, i.e., increases in pulmonary resistance (RL) and decreases in dynamic lung compliance (CDYN), were accomplished by aerosols of prostaglandin F2‐alpha (PGF2α) and histamine (HIST) after a six‐month chronic inhalation study using 500 ppm SO2. Pretreatment with a lidocaine aerosol (2.0%; 30 breaths) failed to produce any inhibition of bronchospasm induced by aerosols of PGF2α or HIST. An IV infusion of hexamethonium (10.0 mg/kg) significantly inhibited PGF2α‐induced percent changes in both RL (226.4 ± 45.2% vs. 134.7 ± 28.7%) and CDYN (52.6 ± 10.8% vs. 35.9 ± 8.8%) but failed to produce significant inhibition against HIST‐induced bronchospasm. These results suggest that the bronchial hyperreactivity attributed to SO2 exposure in our model is probably due in fact to an increased sensitivity of the afferent portion of the cholinergic pathway due to lidocaine's failure to provide inhibition at this site. No change occurs at the ganglia based on the similar action of hexamethonium in this study as to previously published work.
Ineffectiveness of a purine analogue, EMD 28422, in two animal tests of anxiolytic action
Authors: Lal Harbans , Gherezghiher Tseggai , Carney John 
Published: January 2005

AbstractEMD 28422 was compared to chlordiazepoxide for antianxiety activity in two behavioral tests known to predict the anxiolytic action of drugs. In the conflict test, male rats were trained to respond for food reinforcement in which some of the reinforced responses also resulted in the delivery of footshock. Treatment of these rats with chlordiazepoxide but not with EMD 28422 antagonized the foot‐shock‐induced suppression of responding. In the drug discrimination test, male hooded rats were trained to discriminate the anxiogenic action of pentylenetetrazol from saline by responding for food reinforcement on one of two levers after pentylenetetrazol treatment (subconvulsant dose) and on the other lever after saline injection. Pretreatment with chlordiazepoxide and not with EMD 28422 antagonized the pentylenetetrazol stimulus. Ineffectiveness of EMD 28422 in both tests sensitive to chlordiazepoxide action suggests lack of anxiolytic efficacy of this drug, despite its reported enhancement of benzodiazepine binding in the brain.
Changes in γ‐aminobutyric acid and glutamic acid decarboxylase in discrete regions of rat brain following lithium administration and withdrawal
Authors: Ahluwalia Pardeep , Grewaal Darshan S. , Singhal Radhey L. 
Published: January 2005

AbstractThe influence of low dose (1 mmol/kg/day) chronic lithium (Li) treatment was studied on γ‐aminobutyric acid (GABA) levels and glutamic acid decarboxylase (GAD) activity in discrete regions of rat brain. In Li‐treated animals, GABA levels of striatum, midbrain, and ponsmedulla were significantly elevated in comparison to controls. Following 2 days of withdrawal from Li, GABA remained significantly higher in midbrain and pons‐medulla, but returned to control values in striatum. Administration of aminooxyacetic acid (AOAA) 1 hr prior to sacrifice produced an approximately twofold increase in regional GABA content in all three experimental groups. The activity of GAD was enhanced in striatum (11%) and pons‐medulla (22%), but decreased slightly in midbrain (5%) of Li‐treated animals. Li withdrawal caused a significant reduction in GAD activity of hypothalamus and pons‐medulla when compared to control or Li‐treated rats. Acute injection of AOAA enhanced GAD activity in midbrain of the Li‐treated animals and hypothalamus of the Li‐withdrawal group. Our data demonstrate that long‐term Li administration and its subsequent withdrawal has differential effects on both GABA and GAD in various regions of rat brain. However, whether these changes brought about by Li are due to its direct effect, or are exerted indirectly through other neurotransmitter systems, needs to be clarified.
Effects of EMD 15,700 and disulfiram on ethanol intake in rats under schedule‐induced polydipsia
Authors: McMillan D. E. 
Published: January 2005

AbstractRats received 196 food pellets per day under a fixed‐time 90‐sec schedule with both 5% (w/v) ethanol and water freely available. More than 80% of the total daily fluid consumption was the 5% ethanol solution. Disulfiram, and a new aldehyde dehydrogenase inhibitor, EMD 15,700, both markedly decreased 5% ethanol intake and slightly increased water intake. These effects lasted for several days. The schedule‐induced polydipsia model of ethanol consumption in rats appears to be sensitive to the effects of drugs that inhibit ethanol intake in man.
Second generation antidepressants: The pharmacological and clinical significance of selected examples
Authors: Maxwell Robert A. 
Published: January 2005

AbstractUntil recently, tricyclic antidepressants and monoamine oxidase inhibitors were the only therapies available for mental depression. These compounds, while effective, have significant cardiovascular and autonomic side effects and it was recognized that there was room for improvement. As a result of the labors of chemists and pharmacologists over the last 10 years, new or “second generation” compounds are being studied in man. Many of these compounds are structurally, biochemically, and pharmacologically distinct from tricyclic compounds and monoamine oxidase inhibitors and therefore hold out the promise of more effective therapy with fewer side effects. As an interesting offshoot of these structural, biochemical, and pharmacological differences it appears that the prevailing catecholamine theory of affective disorders and of the mode of action of therapeutic agents is challenged. Iprindole, mianserin and bupropion are discussed as examples of second generation antidepressants.
Dopamine receptor agonists in cardiovascular therapy
Authors: Lokhandwala Mustafa F. , Barrett Richard J. 
Published: January 2005

AbstractDopamine receptor agonists exert marked cardiovascular and renal actions that result from activation of specific dopamine receptors located at various sites within the cardiovascular system. The presence of at least two distinct subtypes of dopamine receptors is reported. (1) Neurotropic dopamine receptors, also referred to as δ2 or DA2 receptors, are located at various sites within the sympathetic nervous system, activation of which leads to inhibition of sympathetic nervous system activity. (2) Postsynaptic dopamine receptors, also referred to as δ1 or DA1 are located on vascular smooth muscles of blood vessels as well as at various sites in the kidney, and their activation causes, vasodilatation, inhibition of aldosterone release, and sodium and water reabsorption. The pharmacological responses to activation of neurotropic and postsynaptic dopamine receptors consist of hypotension, bradycardia, diuresis, and natriuresis. Since an elevated sympathetic nervous system activity and retention of salt and water appear to be responsible for several cardiovascular disorders, it is proposed that dopamine receptor agonists may represent a novel class of therapeutic agents for the treatment of certain cardiovascular diseases.Further research efforts in this area are required to understand better the role of endogenous dopamine and dopamine receptors in the maintenance of cardiovascular homeostasis and to develop more selective compounds for experimental and clinical studies in different disease states.
Comparison of the cardiovascular effects of intravenously administered GABA, THIP, and isoguvacine in the anesthetized rat
Authors: Mesdjian E. , DeFeudis F. V. , Jadot G. , Valli M. , Brugerolle B. , Bouyard P. 
Published: January 2005

AbstractMean arterial blood pressure and heart rate were monitored in pentobarbital‐anesthetized rats after intravenous injections of GABA, THIP, or isoguvacine‐HCl (all at 0.1–100 mg/kg). GABA produced dose‐dependent hypotension and bradycardia; THIP produced no appreciable effect on either parameter; and isoguvacine produced hypotension, but no marked change in heart rate. The transient hypotension and bradycardia produced by GABA (1 mg/kg) were partially blocked by pretreatment of the animals with bicuculline or bicuculline‐methobromide. After pretreatment with bicuculline or bicuculline‐methobromide, the hypotensive effect of isoguvacine (1 mg/kg) occurred more rapidly (i.e., during the first 5 min, rather than during 5–15 min after injection of isoguvacine). As THIP penetrates the blood‐brain barrier more readily than GABA or isoguvacine, as GABA and isoguvacine exerted more pronounced cardiovascular effects than THIP, and as bicuculline and bicuculline‐methobromide affected the cardiovascular actions of GABA and isoguvacine, it is suggested that activation of peripheral GABA receptors might explain part of the cardiovascular effects produced by intravenously injected GABA. Further study of isoguvacine and its derivatives might lead to the development of hypotensive (antihypertensive) agents that act on peripheral GABA‐ergic systems.
Effect of a prostaglandin analogue, SC‐30249, on canine gastric secretion
Authors: Dajani Esam Z. , Driskill Doyle R. , Bianchi Robert G. , Phillips Esther L. , Woods Emmett M. , Colton Douglas G. , Collins Paul W. , Pappo Raphael 
Published: January 2005

AbstractWe previously reported the prostagladin analogue SC‐29333 [(±)(16RS)‐15‐deoxy‐16 hydroxy,‐16‐methyl prostaglandin E1 methyl ester] to be a potent inhibitor of gastric secretion in animals. SC‐29333 is comprised of four stereoisomers in approximately equal proportions. It is believed the major antisecretory activity of SC‐29333 results from one isomer, SC‐30249 (16S‐16‐hydroxy‐16‐methyl, 15‐deoxy‐PGE1 methyl ester). Our purpose was to investigate the canine gastric antisecretory action of SC‐30249 relative to SC‐29333. The studies were carried out in maximally stimulated (histamine) Heidenhain pouch (HP) and gastric fistula (GF) dogs. Administered intravenously (i.v.) to HP dogs at the steady‐state plateau of gastric secretion, SC‐30249 was found to be approximately three times more potent than SC‐29333. Administered intragastrically to GF dogs, SC‐30249 is approximately ten times more potent as an inhibitor of gastric secretion than SC‐29333. SC‐30249 (1.0 μg/kg, i.v.) completely inhibited meal‐stimulated gastric secretion but had no significant effect on postprandial serum gastrin concentration. SC‐30249 shared with SC‐29333 the capability of totally antagonizing the histamine‐stimulated gastric secretion in HP dogs without reducing gastric mucosal blood flow. These studies indicate that SC‐30249 is a potent gastric antisecretory agent that merits clinical evaluation.
Meperidine and normeperidine convulsions in mice: Possible opiate and serotonergic mechanisms
Authors: Bader Steven Roy , Moore Paul A. 
Published: January 2005

AbstractThe effects of naloxone and 5‐hydroxytryptophan (5‐HTP) pretreatment on convulsions induced by meperidine and normeperidine were studied in male Swiss‐Webster mice. The CD50 (95% confidence limits) was found to be 17.5 mg/kg (15.6–19.6) for meperidine and 38.0 mg/kg (36.2–39.9) for normeperidine administered intravenously. Convulsions induced by meperidine (17.5 mg/kg) were significantly attenuated by naloxone (30 mg/kg) pretreatment but not by 5‐HTP pretreatment alone. Normeperidine (38.0 mg/kg) induced convulsions were significantly attenuated by 5‐HTP pretreatment, but not by naxolone pretreatment. The administration of a combined dose of meperidine and normeperidine does not produce a supra‐additive response.
Enhancement of benzodiazepine binding by progabide (SL 76002) and SL 75102
Authors: Koe B. Kenneth 
Published: January 2005

AbstractThe new GABA derivatives, progabide (SL 76002) and SL 75102 (the corresponding carboxylic acid), enhanced [3H]diazepam binding to rat cortical membranes. SL 75102 was as effective as GABA, and both were less active than muscimol. Similar to other GABA agonists, progabide and SL 75102 enhanced binding in vitro by an increase in affinity. The elevation of [3H]diazepam binding in the presence of SL 75102 was antagonized by bicuculline. In ex vivo experiments, brain membrane preparations of mice pretreated with progabide were found to bind a greater amount of [3H]diazepam. This increased binding was characterized by an elevation in Bmax, while KD was unaffected. [3H]Flunitrazepam binding to brain in vivo was also enhanced in mice pretreated with progabide. Other GABA agonists (muscimol, THIP, isoguvacine) and GABAergic agents (sodium valproate) elicited an increase in [3H]flunitrazepam binding in vivo. Binding of intravenous [3H]flunitrazepam in vivo may be useful for discovering enhancers of benzodiazepine binding.
Effects of anticholinergic drugs on learning and memory
Authors: Spencer David G. , Lal Harbans 
Published: January 2005

AbstractDeclines in cognitive function during normal aging and in dementic disorders have frequently been hypothesized to involve a decline in cholinergic transmission in the brain. Muscarinic cholinergic receptor blockade produces behavioral effects in animals reminiscent of aging‐related performance deficits. The purpose of the present review is to analyze the results of previous behavioral experiments with antimuscarinic drugs in order to generate an hypothesis of the cognitive effects of muscarinic blockade. Given this hypothesis, it is suggested that experiments may be designed in which the antagonism of antimuscarinic drug effects may be used in the development of geriatric and antidementic drugs.
The effect of several “new and novel” cardiotonic agents on key subcellular processes involved in the regulation of myocardial contractility: Implications for mechanism of action
Authors: Weishaar Ronald E. , Quade Mary , Boyd Denise , Schenden Janet , Marks Steven , Kaplan Harvey R. 
Published: January 2005

AbstractThe effect of several recently synthetized cardiotonic agents on a variety of key metabolic processes involved in regulating calcium homeostasis in the cardiac cell was evaluated in an effort to determine the mechanism of action of these compounds. The agents examined were amrinone, WIN 47,203, AR‐L 57, AR‐L 115 (vardax), carbazeran, and RMI 82,249. The results of this study indicate that amrinone and vardax, at concentrations that stimulate myocardial contractility, have no effect on calcium transport, uptake or EGTA‐induced calcium release from isolated sarcoplasmic reticulum vesicles, or on mitochondrial calcium transport or uptake. Amrinone, vardax, and RMI 82,249 also have no effect on mitochondrial respiration. AR‐L 57 and vardax, but not amrinone, WIN 47,203, or carbazeran, inhibit cardiac Na+, K+‐ATPase activity (IC50 = 140 μM and approximately 1,000 μM, respectively). All of the agents examined inhibit phosphodiesterase activity; WIN 47,203 and carbazeran are the most potent inhibitors, and amrinone, the least. Vardax, amrinone, and carbazeran also potentiate the inotropic response to the beta‐receptor stimulant isoproterenol, and these three agents, in addition to WIN 47,203, also elevate cyclic AMP levels in isolated rabbit papillary muscles. These results indicate that inhibition of phosphodiesterase activity may represent the cardiotonic mechanism of action of amrinone, WIN 47,203, and carbazeran, and perhaps AR‐L 57 and vardax as well. Further studies are required to establish the degree to which Na+, K+‐ATPase inhibition or other actions are also involved in the cardiotonic activity of AR‐L 57 and vardax.
Failure of repeated peer separations to induce depression in infant rhesus monkeys
Authors: Porsolt Roger D. 
Published: January 2005

AbstractThree rhesus monkeys (two female, one male) were separated from their mothers shortly after birth and were brought up together in a group cage. After 90 days together, they were subjected to eight repeated separations of 4–6 days during which they were housed in individual cages. Separations 7 and 8 were preceded by “vertical chamber” confinement of 3 and 8 days, respectively. Separation caused a marked increase in vocalizations. Although at times signs of depression (decreased locomotion, huddling) were apparent, they were neither frequent nor stable and did not seem to depend on either the length or the number of separations. It was concluded that social separation, although inducing clear signs of distress, does not invariably cause depression in infant rhesus monkeys.
Central effects and effective dose determination of suriclone (double‐blind, controlled, phase I safety and quantitative pharmaco‐EEG study)
Authors: Itil Turan M. , Menon Gopi N. , Dreyfus Jean‐Francois , Bozak M. Mahir , Songar Ayhan , Lucadamo Frank 
Published: January 2005

AbstractSuriclone, a nonbenzodiazepine drug, shown to be anxiolytic in animal pharmacology, was investigated within a single dose tolerance and efficacy study using quantitative pharmaco‐EEG. The investigation showed that suriclone is tolerable in single oral doses of up to 0.8 mg, the highest dose given in healthy volunteers. The minimum effective dose producing statistically significant CNS action was 0.3 mg. Suriclone produced significant dose‐ and time‐related CNS effects. The onset of these effects was later than that of diazepam and its duration of action was longer. Suriclone was classified by the HZI computer EEG drug data base as anxiolytic at high doses. Among a variety of anxiolytics, the CNS effect of suriclone was most similar to that of diazepam. The optimal anxiolytic effective single dose of suriclone was predicted to be 0.6 mg.
Pharmacological profiles of two new angiotensin‐converting enzyme (ACE) inhibitors: CGS 13945 and CGS 13934
Authors: Chen Dong‐Sheng , Watkins Barry E. , Ku Edmond C. , Dotson Ronald A. , Burrell Richard D. 
Published: January 2005

AbstractCGS 13945 and CGS 13934 are two nonthiol ACE inhibitors having novel chemical structures. CGS 13945 is a monoester derivative of the free dicarboxylic acid CGS 13934. Based on studies from in vitro inhibition of ACE and in vivo inhibition of angiotensin I pressor responses, CGS 13945 must be hydrolyzed to CGS 13934 to express its optimal biological activity. Studies with rats reveal that CGS 13945 and CGS 13934 are orally effective inhibitors of ACE. Both inhibitors have a longer duration of action and are somewhat less effective than captopril. After oral administration, the bioavailability of the monoester CGS 13945 is greater than that of the free dicarboxylic acid CGS 13934. In the dog, CGS 13934 (i.v.) effectively inhibits angiotensin I pressor responses, but the esterified compound (CGS 13945) has only weak activity. This difference is presumably due to limited hydrolytic capacity of endogenous plasma esterase(s) in this species. However, both CGS 13945 and CGS 13934 potentiate the vasodepressor responses to bradykinin without affecting angiotensin II pressor responses.
The castor oil test in rats: An in vivo method to evaluate antipropulsive and antisecretory activity of antidiarrheals?
Authors: Niemegeers C. J. E. , Awouters F. , Janssen P. A. J. 
Published: January 2005

AbstractCastor oil‐induced diarrhea in rats is described to be an appropriate model of the complex, prolonged processes of hypersecretion and accelerated transit that characterize secretory diarrhea. Suprofen, a prostaglandin biosynthesis inhibitor, was found to postpone diarrhea over a wide dose range, but suprofen failed to reduce the diarrheal excretion. In contrast to suprofen, loperamide not only increased the diarrhea‐free period but also produced a dose‐related decrease of the diarrheal excretion.
(Na+‐K+)‐ATPase inhibitors: Implications for new drug discovery
Authors: Shlevin Harold H. 
Published: January 2005

AbstractThe (Na+‐K+)‐ATPase is a ubiquitous membrane‐bound enzyme that actively transports Na+ out of the cell in exchange for a smaller ratio of extracellular K+. The current report focuses on the role of modifiers of (Na+‐K+)‐ATPase activity in the development of new pharmacological agents. More versatile biological test systems are proposed. Possible use of Na+‐K+‐ATPase activity modulators in treatment of hypertension and other diseases are discussed. It is concluded that the ubiquitous distribution and crucial role of the enzyme in normal and diseased cell function merits a critical biological and chemical reappraisal of the enzyme beyond the current narrow viewpoint dealing with the application of glycosides in the treatment of congestive heart failure.
Angiotensin II antagonists—saralasin
Authors: Moore Alan F. , Fulton Robert W. 
Published: January 2005

AbstractSaralasin is the only marketed member of a class of compounds described as angiotensin II receptor antagonists. Its pharmacology is characterized by three general properties: (1) no actions unrelated to the renin‐angiotensin system; (2) a small partial agonist effect in some tissues in vitro and in some animal models in vivo, and (3) a blood‐pressure lowering response to saralasin evident only in animals with an activated endogenous renin angiotensin system. It is suggested that the natriuretic effect of angiotensin II mediated via central nervous system (CNS) mechanisms may be future productive area of research in which to study the actions of angiotensin II antagonists.
The 5‐HT syndrome in rats as tool for the screening of psychoactive drugs
Authors: Ortmann R. 
Published: January 2005

AbstractThe use of the behavioral 5‐HT syndrome in rats to characterize psychoactive drugs interacting with the central serotonin system is described. The potentiation of L‐5‐HTP‐induced excitation can be used to detect drugs inhibiting central monoamine oxidase (MAO) A or the 5‐HT uptake system and to define their mechanism of action. In addition to their potency, the biological half‐life of these types of drugs can also be measured. The mechanism of action by which β‐adrenoceptor agonists like salbutamol or clenbuterol potentiate behavioral effects of L‐5‐HTP is discussed. The 5‐HT syndrome is also a convenient behavioral test system to screen for central 5‐HT antagonists and 5‐HT agonists. Different procedures to characterize the 5‐HT specificity of behavioral effects induced by putative 5‐HT agonists are described and their relevance discussed.