Salmi P, Karlsson T, Ahlenius S
Department of Behavioural Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Eur J Pharmacol. 1994 Feb 21;253(1-2):67-73. doi: 10.1016/0014-2999(94)90758-7.
Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
氯氮平（7.5 - 30.0 μmol kg⁻¹，皮下注射）可使大鼠体温降低。氯氮平（7.5 μmol kg⁻¹，皮下注射）引起的体温降低被选择性多巴胺D1受体拮抗剂SCH 23390（0.3 μmol kg⁻¹，皮下注射）完全拮抗，而选择性多巴胺D2受体拮抗剂雷氯必利（1.6 μmol kg⁻¹，皮下注射）则产生部分拮抗作用。另一方面，α-肾上腺素能受体拮抗剂（咪唑克生和哌唑嗪）、5-羟色胺受体拮抗剂（(-)-吲哚洛尔和利坦色林）或毒蕈碱M1受体拮抗剂东莨菪碱均不能拮抗这种体温降低。5-羟色胺1C/2受体激动剂DOI（0.75 μmol kg⁻¹）引起的体温过高被氯氮平（3.0 μmol kg⁻¹，皮下注射）阻断。氯氮平不能拮抗选择性多巴胺D1和D2受体激动剂（A 68930和喹吡罗）、α2-肾上腺素能受体激动剂可乐定、5-羟色胺1A受体激动剂8-OH-DPAT（8-羟基-2-(二正丙基氨基)四氢萘）或毒蕈碱M1受体激动剂氧化震颤素引起的体温降低。目前的结果表明，氯氮平可能是脑多巴胺D1受体的部分激动剂。
