Hirano Shoko, Miyata Shigeo, Onodera Kenji, Kamei Junzo
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Eur J Pharmacol. 2007 May 7;562(1-2):72-6. doi: 10.1016/j.ejphar.2007.01.063. Epub 2007 Feb 8.
It has been reported that chlorpheniramine, a classical antihistamine, has antidepressant-like effects in animal models of depression. In this study, we examined the involvement of dopaminergic (dopamine D(1) and dopamine D(2) receptors), noradrenergic (alpha(1)- and beta-adrenoceptors) and serotonergic (5-HT(1A) and 5-HT(2) receptors) receptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test. We also investigated the involvement of these monoamine receptors in the antidepressant-like effect of imipramine for comparison with the mechanisms of the effect of chlorpheniramine. Both imipramine and chlorpheniramine significantly reduced the duration of immobility in the tail suspension test without affecting spontaneous locomotor activity in mice. The anti-immobility effect of imipramine (30 mg/kg, i.p.) was significantly antagonized by the selective dopamine D(1) receptor antagonist SCH23390 but not by the other receptor antagonists. In contrast, the anti-immobility effect of chlorpheniramine was significantly inhibited by SCH23390 and the selective alpha(1)-adrenoceptor antagonist prazosin, but not by the other receptor antagonists. In conclusion, these results suggest that chlorpheniramine exerts an antidepressant-like effect in the mouse tail suspension test that is mediated by at least the activation of dopamine D(1) receptors and alpha(1)-adrenoceptors. In addition, the antidepressant-like effect of chlorpheniramine may be induced by several mechanisms that are different from those involved in the antidepressant-like effect of imipramine.
据报道，经典抗组胺药氯苯那敏在抑郁症动物模型中具有抗抑郁样作用。在本研究中，我们在小鼠悬尾实验中检测了多巴胺能（多巴胺D1和多巴胺D2受体）、去甲肾上腺素能（α1和β肾上腺素能受体）和5-羟色胺能（5-HT1A和5-HT2受体）受体在氯苯那敏抗抑郁样作用中的参与情况。为了与氯苯那敏的作用机制进行比较，我们还研究了这些单胺受体在丙咪嗪抗抑郁样作用中的参与情况。丙咪嗪和氯苯那敏均能显著缩短小鼠悬尾实验中的不动时间，且不影响小鼠的自发运动活性。丙咪嗪（30mg/kg，腹腔注射）的抗不动作用被选择性多巴胺D1受体拮抗剂SCH23390显著拮抗，但不被其他受体拮抗剂拮抗。相比之下，氯苯那敏的抗不动作用被SCH23390和选择性α1肾上腺素能受体拮抗剂哌唑嗪显著抑制，但不被其他受体拮抗剂抑制。总之，这些结果表明，氯苯那敏在小鼠悬尾实验中发挥抗抑郁样作用，至少是由多巴胺D1受体和α1肾上腺素能受体的激活介导。此外，氯苯那敏的抗抑郁样作用可能由几种不同于丙咪嗪抗抑郁样作用的机制诱导产生。
