Animal and Clinical Pharmacologic Techniques in Drug Evaluation

Nodine, John H.; Siegleh, Peter E.

doi:10.1097/00000542-196505000-00024

Cited by 18 publications

(4 citation statements)

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“…The exact mechanism by which perphenazine induces rigidity, akinesia and depression is not fully understood at present but because of antiadrenergic properties, it can be expected that catecholamines play a role (8). The failure of tricyclic antidepressants in preventing perphenazine induced parkinson-like signs could possibly be due to inability to change the monoamine concentration in the body (9).…”

Section: Discussionmentioning

confidence: 99%

The Influence of Monoamine Oxidase Inhibitors and Some Other Antidepressants on the Antiparkinsonian Activity of Sub-Effective Doses of Diphenylhydramine in Rats and Mice

Patni

Dandiya

1972

Jpn.J.Pharmacol

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Our earlier observations(1) with antidepressants (MAOIs and tricyclic) in protecting drug-induced Parkinson-like signs in animals showed that these agents were not so effective as the commonly employed antiparkinsonian drugs. It was, therefore, decided to combine these antidepressants i.e. sub-effective doses of these together with sub-effective doses of the commonly used antiparkinsonian drugs, in order to assess the therapeutic efficacy of such combinations, as undersirable sedative effects of antiparkinsonian drugs may be counteracted by antidepressants.In the present study such combinations with the well established anti parkinsonian drug, diphenylhydramine, were used and the degree of protection from parkinson-like signs induced by tremorine in mice and perphenazine in rats, were observed. MATERIALS AND METHODSAnimal and drugs: Albino rats (125 to 175 g) and mice (25 to 40 g) of Haffkine strain were used. The drugs employed were diphenylhydramine hydrochloride (5 mg,/kg); MAOIs such as, t-methyltryptamine acetate (10 mg/kg), a-ethyltryptamine acetate (10 mg/kg), phenelzine sulphate (5 mg/kg); tricyclic antidepressants (20 mg/kg) like, protriptyline hydro chloride, nortriptyline hydrochloride, proheptatriene hydrochloride, prothiadene hydro chloride, and hydrothiadene maleate. All drugs were administered intraperitoneally. A group of 10 rats or 10 mice was employed for each drug or drug combination. Solutions: Perphenazine was dissolved in to a drop of N/10 HCI, diluted with di stilled water and the pH adjusted to 6 with dilute N/10 NaOH before the required volume was made. All other drugs were dissolved in to distilled water. The volume administered was kept constant i.e. 4 ml/kg for rats and 10 ml/kg for mice. Pretreatment:The animals were pretreated for 15 min with diphenylhydramine; a methyltryptamine and a'-ethyltryptamine 30 min; phenelzine 18 hr and all tricyclic antide pressants 30 min before administration of perphenazine or tremorine. Perphenazine technique: The technique employed was essentially the same as des cribed by Morpurgo (2). Effects were evaluated at various tines by the following proced dure a modification of that described by Dandiya and Bhargava (1).

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Section: Discussionmentioning

confidence: 99%

The Influence of Monoamine Oxidase Inhibitors and Some Other Antidepressants on the Antiparkinsonian Activity of Sub-Effective Doses of Diphenylhydramine in Rats and Mice

Patni

Dandiya

1972

Jpn.J.Pharmacol

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“…23.5 27.7 g) mice were monitored. According to the modified method of Irwin et al, 9 the general behaviours such as locomotor activity, Straub's tail response, tremors, convulsion, abdominal tone, catalepsy, motor cord, righting reflex, grip strength, pinna reflex, piloerection, skin colour, respiration rate, palpebra size, exophthalmos, lacrimation, salivation, diarrhea and mortality were observed at 0, 30, 60, 120, 360 min and 24 hours after the test substance administration.…”

Section: General Behaviourmentioning

confidence: 99%

Safety pharmacology of sibutramine mesylate, an anti-obesity drug

2005

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Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague / respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbitalinduced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric / Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

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“…Many books have now been written which conveniently mass together and discuss the many techniques which can be used during tertiary evaluation to pharmacologically and toxicologically define the activity of a drug (Ther, 1948;Burn, 1952;Smith, 1961;Laurence and Bacharach, 1964;Nodine and Siegler, 1964;Turner, 1965;Siegler and Moyer, 1967;Perry et al, 1968;McLeod et al, 1970;Turner and Hebborn, 1971;Domer, 1971;Schwartz, 1971;Chignell, 1972;Danile and Paton, 1975). These extremely useful "idea" books allow for the experimental definition of all drug types --except the unique new drug.…”

Section: E Tertiary Evaluationmentioning

confidence: 99%

Pharmacological Approaches to Natural Product Screening and Evaluation

Malone¹

1977

Proceedings in Life Sciences

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Animal and Clinical Pharmacologic Techniques in Drug Evaluation

Cited by 18 publications

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The Influence of Monoamine Oxidase Inhibitors and Some Other Antidepressants on the Antiparkinsonian Activity of Sub-Effective Doses of Diphenylhydramine in Rats and Mice

The Influence of Monoamine Oxidase Inhibitors and Some Other Antidepressants on the Antiparkinsonian Activity of Sub-Effective Doses of Diphenylhydramine in Rats and Mice

Safety pharmacology of sibutramine mesylate, an anti-obesity drug

Pharmacological Approaches to Natural Product Screening and Evaluation

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