Similarities in the pharmacology of spontaneous and DOI-induced head-shakes suggest 5HT2A receptors are active under physiological conditions.
Nine monoamine receptor antagonists have been compared for their potency to inhibit both spontaneously occurring and DOI ((1-)2,5-dimethoxy-4-iodophenyl)-2-aminopropane)-induced head-shakes (HS). Ritanserin, ketanserin, prazosin, haloperidol, pimozide, SCH 23390 and SCH 39166 potently and dose-dependently antagonised both types of HS while sulpiride and raclopride produced weak and partial antagonism. The potency of these agents to inhibit spontaneous HS and DOI-induced HS was closely correlated (r = 0.94) and was significantly related to 5HT2A receptor and to alpha 1-adrenoceptor affinities taken from published sources. Potency was independent of affinity for D2 receptors but there was a possible influence of D1 receptor affinity. HS have been proposed to model Tourette's Syndrome; thus the present findings may have implications for the mechanism of action of antipsychotic agents in this condition and possibly also in schizophrenia. Contrary to previous suggestions, 5HT2A receptors may be tonically activated under physiological conditions.
Dursun
S M
SM
Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK.
Handley
S L
SL
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000662:Amphetamines / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D017982:Receptors, Biogenic Amine / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*
D000317:Adrenergic alpha-Antagonists; D000662:Amphetamines; D018492:Dopamine Antagonists; D017982:Receptors, Biogenic Amine; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine