Clozapine--a serotonin antagonist? 1984

H Fink, and R Morgenstern, and W Oelssner

The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.

UI MeSH Term Description Entries
D008238 Lysergic Acid Diethylamide Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood. LSD,Lysergide,LSD-25,Lysergic Acid Diethylamide Tartrate,Acid Diethylamide, Lysergic,Diethylamide, Lysergic Acid,LSD 25
D008297 Male Males
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009714 Nucleus Accumbens Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA. Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
D010646 Phentolamine A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. Fentolamin,Phentolamine Mesilate,Phentolamine Mesylate,Phentolamine Methanesulfonate,Phentolamine Mono-hydrochloride,Regitine,Regityn,Rogitine,Z-Max,Mesilate, Phentolamine,Mesylate, Phentolamine,Methanesulfonate, Phentolamine,Mono-hydrochloride, Phentolamine,Phentolamine Mono hydrochloride
D011903 Raphe Nuclei Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA. Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003000 Clonidine An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION. Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D003024 Clozapine A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Clozaril,Leponex

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