Modified Method for Studying Anorexigenic Agents in Dogs

Adams, H.J.; Greene, Leon

doi:10.1002/jps.2600531128

Cited by 5 publications

(1 citation statement)

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“…The slope of the line of a plot of duration of effect versus logarithm of dose is equal to 2.303jk and thereby permits an estimation of the elimination rate constant (k). This linear relationship has been demonstrated with respect to the hyp notic effect of glutethimide and diallyl-barbituric acid in human subjects who took toxic doses of these drugs (38), the anorexigenic effect of dex troamphetamine sulfate in dogs (40), the general anesthetic effect of keta mine in human subjects (21), the general anesthetic effect of phencyclidine and pentobarbital in monkeys (21), the neuromuscular blocking effect of succinylcholine in man (41), and the anticoagulant effect of heparin in man (26). In the case of succinylcholine and heparin it has been possible to esti mate elimination rate constants not only from the duration-log dose relationship, but also from the rate of decline of the effect following adminis tration of a single dose (26,41) .…”

Section: Single Compartment Kineticsmentioning

confidence: 81%

Pharmacokinetics of Drug Action

Lévy¹,

Gibaldi²

1972

Annu. Rev. Pharmacol.

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This is a review of the literature since 1960 on the kinetics of reversible pharmacologic effects in intact animals including man. No claim is made that this is a complete survey. It is practically impossible to conduct an effective literature search on the pharmacokinetics of drug action, since ti tles of papers and index terms do not usually indicate that the investigations are concerned with the time course of pharmacologic effects in relation to dose or drug concentrations. The kinetics of drug absorption, distribution, and elimination are not included in this review. The literature in this field has been reviewed only recently (1) and this subject has been dealt with in a number of recently published books (2-4). This review will consist of four sections. These will summarize the literature on the relationship be tween drug concentration and pharmacologic effect, the kinetics of drug ac tion in cases where the body can be characterized as a single compartment, the kinetics of drug action when the body acts as a multi-compartment sys tem, and the kinetics of indirect pharmacologic effects. While there has been some theoretical work on these subjects before 1960, most of the ex perimental studies and the quantitative correlations between the time course of drug levels in the body and the time course of pharmacologic effects have been carried out since then. These investigations were made possible largely by the extensive progress in analytical and computational methodology as well as in the ability to quantitate certain pharmacologic effects in animals and man. DRUG CONCENTRATION AND PHARMACOLOGIC EFFECTThe concept of a direct and rapidly reversible pharmacologic effect im plies that a given intensity of effect is associated with a particular drug concentration at the site of action. Consequently, there is likely to be a cor responding relationship between the intensity of a pharmacologic effect and the post-distributive concentration of drug in plasma or serum. For exam ple, in studies of individual differences in the effect of drugs in relation to drug concentration in tissues of rats, it has been found that the duration of narcosis produced by a constant dose of pentobarbital sodium differed widely in different rats. However the concentrations of pentobarbital in the brain and serum of these rats upon awakening showed no such differences 85 6529 Annu. Rev. Pharmacol. 1972.12:85-98. Downloaded from www.annualreviews.org Access provided by University of Sussex on 08/19/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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Section: Single Compartment Kineticsmentioning

confidence: 81%

Pharmacokinetics of Drug Action

Lévy¹,

Gibaldi²

1972

Annu. Rev. Pharmacol.

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Theoretical Relationship Between Dose, Elimination Rate, and Duration of Pharmacologic Effect of Drugs

Levy

Nelson

1965

Journal of Pharmaceutical Sciences

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Profil psychopharmacologique d'un nouvel agoniste Dopaminergique, le RU 24213

Boissier¹,

Dumont²,

Laurent³

et al. 1980

Psychopharmacology

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The psychopharmacological properties of RU 24213 were compared to those of other dopaminergic agonists (apomorphine, dexamphetamine, bromocriptine and L-dopa) in various behavioural tests. In naive mice the drug reduced the locomotor hyperactivity in the primary exploratory phase and produced stimulation in the subsequent stabilized activity period. In rats it provoked dose-related stereotypies, specially gnawing and sniffing. It delayed the cataleptic state induced by prochlorperazine without affecting its intensity. In animals unilaterally lesioned with 6-OHDA in the nigro-striatal pathway, RU 24213 caused contralateral turning. It exhibited relatively weak emetic and anorexic effects in dogs. Core temperature recordings in rats revealed a biphasic hypo- and hyperthermic activity. In drug interaction studies it was obsers in rats with unilateral electrolytical striatal lesion. The results obtained suggest that RU 24213 stimulates dopamine receptors both directly and indirectly. In this respect it could be compared to bromocriptine but unlike this latter compound it has an immediate effect which is of shorter duration.

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Modified Method for Studying Anorexigenic Agents in Dogs

Cited by 5 publications

References 1 publication

Pharmacokinetics of Drug Action

Pharmacokinetics of Drug Action

Theoretical Relationship Between Dose, Elimination Rate, and Duration of Pharmacologic Effect of Drugs

Profil psychopharmacologique d'un nouvel agoniste Dopaminergique, le RU 24213

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