Interaction of clozapine with the histamine H3 receptor in rat brain.
We examined possible interactions between neuroleptics and the histamine H3 receptor and found an interaction of clozapine with this receptor. In competition binding experiments, using the H3 antagonist, [125I]-iodophenpropit, we observed a Ki of 236 +/- 87 nM. Functionally, clozapine was studied on the H3-mediated inhibition of [3H]-5-hydroxytryptamine ([3H]-5-HT) release from rat brain cortex slices. Clozapine acts as an antagonist with an apparent KB value of 79.5 nM.
Rodrigues
A A
AA
Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, N.Y. 10029, USA.
Jansen
F P
FP
Leurs
R
R
Timmerman
H
H
Prell
G D
GD
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism
D006633:Histamine Antagonists; D007093:Imidazoles; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; D007550:Isothiuronium; C077791:iodophenpropit; C069357:alpha-methylhistamine; C052075:thioperamide; D003024:Clozapine; D006220:Haloperidol