Tatarczyńska Ewa, Antkiewicz-Michaluk Lucyna, Kłodzińska Aleksandra, Stachowicz Katarzyna, Chojnacka-Wójcik Ewa
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Cracow PL 31-343, Poland.
Eur J Pharmacol. 2005 May 23;516(1):46-50. doi: 10.1016/j.ejphar.2005.04.025.
The mechanism of the antidepressant-like activity of the selective 5-hydroxytryptamine(1B) (5-HT(1B)) receptor agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP 94253) was studied in the forced swimming test in mice. CP 94253 administered intraperitoneally at a single dose of 5 mg/kg potently shortened the immobility time of mice. The anti-immobility effect of CP 94253 was wholly blocked by the selective 5-HT(1B) receptor antagonist N-[3-(2-dimethylamino)ethoxy-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide (SB 216641, 5 mg/kg), the dopamine D2-like receptor antagonist sulpiride (50 mg/kg) and the alpha(2)-adrenoceptor antagonist idazoxan (2 mg/kg), but was not modified in animals with a lesion of the 5-HT system produced by p-chlorophenylalanine (p-CPA, 3 x 300 mg/kg). The obtained results suggest that the anti-immobility effect of CP 94253 is mediated by activation of 5-HT(1B) receptors-most probably located postsynaptically and/or as heteroreceptors, and that the dopamine and the noradrenaline systems are involved in this action.
在小鼠强迫游泳试验中研究了选择性5-羟色胺（1B）（5-HT（1B））受体激动剂5-丙氧基-3-（1,2,3,6-四氢-4-吡啶基）-1H-吡咯并[3,2-b]吡啶（CP 94253）的抗抑郁样活性机制。腹腔注射单剂量5mg/kg的CP 94253可有效缩短小鼠的不动时间。CP 94253的抗不动作用完全被选择性5-HT（1B）受体拮抗剂N-[3-（2-二甲基氨基）乙氧基-4-甲氧基苯基]-2'-甲基-4'-（5-甲基-1,2,4-恶二唑-3-基）-（1,1'-联苯）-4-甲酰胺（SB 216641，5mg/kg）、多巴胺D2样受体拮抗剂舒必利（50mg/kg）和α（2）-肾上腺素能受体拮抗剂咪唑克生（2mg/kg）阻断，但在对氯苯丙氨酸（p-CPA，3×300mg/kg）造成5-HT系统损伤的动物中未改变。所得结果表明，CP 94253的抗不动作用是通过激活5-HT（1B）受体介导的——最可能位于突触后和/或作为异受体，并且多巴胺和去甲肾上腺素系统参与了这一作用。
