Department of Psychiatry, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Psychopharmacology (Berl). 2009 Nov;207(1):119-25. doi: 10.1007/s00213-009-1639-8. Epub 2009 Aug 18.
Substantial increases in body weight can be induced by several antipsychotic drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly 5-HT2C and histamine H1 receptors, is implicated in this effect.
We have investigated the contribution of effects at these receptors to olanzapine-induced weight gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight female rats.
Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg), but not the histamine H1 antagonist mepyramine (1 mg/kg), produced significant increases in percentage body weight above vehicle; olanzapine showed a significantly greater effect than SB 243213. Haloperidol (0.1 mg/kg) alone or with mepyramine had no significant effects on weight gain, while with SB 243213 and with both SB 243213 and mepyramine, it showed olanzapine-like increases in weight.
These results suggest that 5-HT2C receptor antagonism or inverse agonism, in the presence of D2 receptor antagonism, may contribute to olanzapine-induced weight gain.
一些抗精神病药物，尤其是奥氮平和氯氮平，可引起体重显著增加。这种作用与某些受体（特别是 5-HT2C 和组胺 H1 受体）的拮抗作用有关。
我们研究了这些受体的作用对奥氮平诱导的体重增加的影响，奥氮平在每天腹腔注射后 5 天内引起体重增加，8 只雌性大鼠分为一组进行实验。
奥氮平（2 mg/kg）和 5-HT2C 拮抗剂 SB 243213（1 mg/kg），而不是组胺 H1 拮抗剂甲吡嗪（1 mg/kg），可显著增加体重百分比；奥氮平的作用明显大于 SB 243213。单独使用氟哌啶醇（0.1 mg/kg）或甲吡嗪对体重增加没有显著影响，而与 SB 243213 合用或与 SB 243213 和甲吡嗪合用，则表现出与奥氮平相似的体重增加。
这些结果表明，5-HT2C 受体拮抗作用或反向激动作用，在 D2 受体拮抗作用的存在下，可能有助于奥氮平引起的体重增加。
