METHOD OF GRAPHICAL ANALYSIS OF 2+2 AND 3+3 BIOLOGICAL ASSAYS WITH GRADED RESPONSES.
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Biological Assay↗
Biomedical subjects
B T WARNER
Publications and source records attributed to B T WARNER.
A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine.
Injection of 5-hydroxytryptophan into mice produces a characteristic head-twitch. For a given period of observation this response may be assessed quantitatively either by observing the proportion of mice showing at least one head-twitch (a quantal response) or by counting the number of head-twitches for each mouse (a graded response). A method, based on the quantal response, of investigating the effect of centrally acting compounds on the head-twitch response is described. Evidence is presented that the head-twitches are due to a central action of 5-hydroxytryptamine formed by decarboxylation of 5-hydroxytryptophan. Head-twitches are potentiated by monoamine oxidase inhibitors and by phenytoin. Antagonists tested include an inhibitor of decarboxylase, antagonists of 5-hydroxytryptamine, some antihistamines, major tranquillizers and analgesic and sympathomimetic drugs. Drugs which neither potentiate nor inhibit the response include barbiturates and minor tranquillizers. The method may be valuable in the preliminary examination of compounds likely to have a central action.
5-Hydroxytryptophan↗
Multiple toe-pinch method for testing analgesic drugs.
In guinea-pigs and rats, an immediate squeak was one of the most consistent and readily observed responses to application of a light artery clip to the base of a toe. Morphine and related drugs suppressed this response. Squeak-responses from each toe of an experimental animal formed the basis of a technique for measuring activity of analgesic drugs. A statistical method was developed to analyse the correlated quantal observations obtained. It provided an estimate of the increase of information from several toes compared with one. Testing all toes of each animal yielded a substantial increase of information, because the correlation between responses of different toes was low. Among drugs having an analgesic action in man, 1-(beta-diethyl-aminoethyl)-2-(p-ethoxybenzyl)-5-nitrobenzimidazole, methadone, morphine, pethidine and codeine (in descending order of potency) were active in this test in guinea-pigs. Acetylsalicylic acid, amidopyrine, amphetamine, chlorpromazine, 4-hydroxyisophthalic acid, lysergic acid diethylamide, mephenesin, nalorphine, pentetrazole, phenobarbitone, phencyclidine, phenytoin, salicylamide, strychnine and troxidone showed little or no activity. The time-courses of active drugs were estimated, and morphine had the longest action.
Aminopyrine↗
Evaluation of antagonists of histamine, 5-hydroxytryptamine and acetylcholine in the guinea-pig.
Changes in the resistance to entry of air into the lungs of anaesthetized guinea-pigs have been used to study the effects of histamine, 5-hydroxytryptamine, and acetylcholine. Some known antagonists of these bronchoconstrictor agents have been investigated. The degree of antagonism has been expressed in terms of the dose ratio, previously used only with in vitro preparations.
Acetylcholine↗