An in vivo pharmacological method for the quantitative evaluation of the central effects of alpha 1 adrenoceptor agonists and antagonists
| Autor: | J. Fitten, A.S. Kling, C.K. Kodama, M.K. Menon |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Nialamide
Male Myoclonus medicine.medical_specialty Dextroamphetamine Apomorphine Phenoxybenzamine Stimulation Pharmacology Levodopa Cellular and Molecular Neuroscience chemistry.chemical_compound Nalidixic Acid Pimozide Postsynaptic potential Internal medicine medicine Prazosin Animals Drug Interactions Naphthyridines Adrenergic alpha-Antagonists Dose-Response Relationship Drug Chemistry Brain Rats Inbred Strains Stereoisomerism Reserpine Cirazoline Rats Amphetamine Endocrinology Adrenergic alpha-Agonists medicine.drug |
| Zdroj: | Neuropharmacology. 25(5) |
| ISSN: | 0028-3908 |
| Popis: | A new in vivo pharmacological method for the quantitative evaluation of alpha 1-adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited myoclonic twitch activity; their effects were dose-related and the d-isomer was approximately 3.5 times more effective than the l-isomer. While pimozide did not block this response, the postsynaptic alpha 1-antagonist prazosin fully blocked the myoclonic twitch activity induced by d-amphetamine. Other postsynaptic alpha 1-antagonists, such as haloperidol, phenoxybenzamine and clozapine, were also effective in blocking this response to d-amphetamine. Since d-amphetamine elicited myoclonic twitch activity in rats pretreated with reserpine and alpha-methyl-p-tyrosine, it was concluded that d-amphetamine exerted a direct alpha 1-adrenoceptor stimulation. In rats pretreated with nialamide and pimozide, l-DOPA elicited myoclonic twitch activity which was dose-related. This effect of l-DOPA was promptly and fully blocked by prazosin. It was concluded that this response to l-DOPA resulted from stimulation of alpha 1-adrenoceptors. The relative potencies of four alpha 1-adrenoceptor stimulants, namely, cirazoline, St-587, (-)SKF 89748A and Sgd 101/75 were determined using this method. The results correlated very well with their relative potencies to increase the diastolic blood pressure of pithed rats. Evidence that myoclonic twitch activity is a centrally-mediated response has also been presented. It appears that the method is a simple, sensitive, versatile and easily quantifiable procedure for the evaluation of the central effects of alpha 1-adrenoceptor agonists and antagonists. |
| Databáze: | OpenAIRE |
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