The citalopram/5-HTP-induced head shake syndrome is correlated to 5-HT2 receptor affinity and also influenced by other transmitters.
Combination of the 5-HT-uptake inhibitor, citalopram, with 1-5-HTP induced a characteristic head shake syndrome in rats. This was blocked by a range of 5-HT antagonists, including the selective 5-HT2 antagonists, ketanserin and pirenperone and was also blocked by the alpha 1-adrenoceptor antagonists, prazosin and WB 4101, and the alpha 2-adrenoceptor agonist, clonidine. 1-5-HTP-antagonistic effect was also recorded for 26 neuroleptic drugs. Their inhibitory potencies showed close correlation to 5-HT2-receptor affinity in vitro and, slightly weaker, to alpha 1-adrenoceptor affinity. In contrast, no correlation to dopamine D-2 receptor affinity was found, indicating that the cataleptogenic and motility-inhibitory properties of neuroleptics did not unspecifically influence 1-5-HTP-induced head shakes. These were not influenced by a histaminic antagonist, muscarinic antagonist or alpha 2-adrenoceptor antagonist, but were inhibited by beta-adrenoceptor blockers, GABA agonists, a benzodiazepine and morphine. The results indicate that 1-5-HTP-induced head shakes are most sensitive to 5-HT2 antagonists, but that the syndrome is influenced by other neuronal systems. Since 5-HT2 affinity and alpha 1-adrenoceptor affinity of many compounds is found concomitantly, caution is needed to evaluate the relative importance of these properties for 1-5-HTP antagonism.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D015283:Citalopram; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016627:Oxidopamine; D011224:Prazosin / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D011438:Propylbenzilylcholine Mustard / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D006633:Histamine Antagonists; D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D011437:Propylamines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D011438:Propylbenzilylcholine Mustard; D013134:Spiperone; D016627:Oxidopamine; D006916:5-Hydroxytryptophan; D000661:Amphetamine; D011224:Prazosin