Wong G, Kuoppamäki M, Hietala J, Lüddens H, Syvälahti E, Korpi E R
Department of Alcohol Research, National Public Health Institute, Helsinki, Finland.
Eur J Pharmacol. 1996 Oct 31;314(3):319-23. doi: 10.1016/s0014-2999(96)00671-1.
Similarly to clozapine, a clozapine metabolite, N-desmethylclozapine, but not clozapine N-oxide, antagonized brain gamma-aminobutyric acid type A (GABAA) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([3H]flunitrazepam) or convulsant (t-[35S]bicyclophosphorothionate) binding sites of the GABAA receptor. The results thus suggest that the GABAA receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine receptors and is unlikely to be involved in the therapeutic actions of clozapine.
与氯氮平类似，一种氯氮平代谢物N - 去甲基氯氮平，但不是氯氮平N - 氧化物，在高微摩尔浓度下拮抗脑γ-氨基丁酸A型（GABAA）受体。然而，每天皮下注射氯氮平（10和25mg/kg）和氟哌啶醇（0.5mg/kg），持续14天，未能改变GABA对大鼠大脑皮质和小脑GABAA受体的苯二氮䓬（[3H]氟硝西泮）或惊厥剂（t - [35S]双环磷硫代酸盐）结合位点的调节作用。因此，结果表明，与氯氮平对某些单胺受体的作用相比，慢性体内氯氮平治疗所产生的GABAA受体拮抗作用较弱，并且不太可能参与氯氮平的治疗作用。
