Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse.

Abstract

Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (--)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (+/-)-propranolol. This effect is probably not related to blockade of beta-adrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically.

• Authors: R Chermat, L Doaré, F Lachapelle, P Simon
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 318 Issue 2 Pg. 94-9 (Dec 1981) ISSN: 0028-1298 [Print] Germany
• PMID: 6276790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Receptors, Adrenergic, alpha
• Receptors, Adrenergic, beta
• Receptors, Dopamine
• Serotonin
• Norepinephrine

Topics

• Animals
• Anticonvulsants (pharmacology)
• Drug Interactions
• Handling, Psychological (physiology)
• Male
• Mice
• Mice, Quaking
• Norepinephrine (physiology)
• Parasympathetic Nervous System (drug effects)
• Receptors, Adrenergic, alpha (drug effects)
• Receptors, Adrenergic, beta (drug effects)
• Receptors, Dopamine (drug effects)
• Seizures (physiopathology)
• Serotonin (physiology)