Przegaliński E, Filip M, Bijak M, Wedzony K, Budziszewska B, Tokarski K, Maćkowiak M, Fijał K
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1996 Jan-Feb;48(1):13-22.
The receptor binding and pharmacological profile of the new, putative 5-HT1A receptor antagonist MP-3022 (4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine) were studied. Another 5-HT1A receptor antagonist, (S)-WAY 100135 ((S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2- phenylpropanamide), was used as a reference drug in functional models. MP-3022 showed a high affinity (Ki) of 25 nM and 69 nM, respectively, at 5-HT1A binding sites and alpha 1-adrenoceptors in vitro. The Ki values of MP-3022 in relation to other binding sites examined (5-HT2A, alpha 2- or beta-adrenoceptors, dopamine D1 and D2) were 20-100-fold lower. In functional studies, MP-3022 significantly attenuated the 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced decrease in the population spike evoked in the CA1 cell layer of the hippocampal slice preparation, without producing its own effects. The 8-OH-DPAT-evoked increase in the corticosterone concentration in the serum as well as the 8-OH-DPAT-mediated decrease in the 5-HT turnover in the hippocampus were attenuated by MP-3022. MP-3022 increased the serum corticosterone concentration only at the highest dose used, but it did not change the 5-HT turnover in the hippocampus. Like MP-3022, (S)-WAY 100135 antagonized the 8-OH-DPAT-induced effects. It has also been demonstrated that (S)-WAY 100135 is devoid of an intrinsic activity at 5-HT1A receptors. The data obtained demonstrate that, like (S)-WAY 100135, MP-3022 behaves like a functional antagonist at pre- and postsynaptic 5-HT1A receptors.
对新型假定的5-HT1A受体拮抗剂MP-3022（4-[3-(苯并三唑-1-基)丙基]-1-(2-甲氧基苯基)哌嗪）的受体结合和药理学特性进行了研究。另一种5-HT1A受体拮抗剂(S)-WAY 100135（(S)-N-叔丁基-3-[4-(2-甲氧基苯基)哌嗪-1-基]-2-苯基丙酰胺）被用作功能模型中的参考药物。MP-3022在体外对5-HT1A结合位点和α1-肾上腺素能受体分别显示出25 nM和69 nM的高亲和力（Ki）。MP-3022相对于其他检测的结合位点（5-HT2A、α2-或β-肾上腺素能受体、多巴胺D1和D2）的Ki值低20-100倍。在功能研究中，MP-3022显著减弱了8-OH-DPAT（8-羟基-2-(二正丙基氨基)四氢萘）诱导的海马脑片制备CA1细胞层群体峰电位的降低，且自身无作用。MP-3022减弱了8-OH-DPAT诱导的血清皮质酮浓度升高以及8-OH-DPAT介导的海马5-HT周转率降低。MP-3022仅在所用最高剂量时增加血清皮质酮浓度，但不改变海马中的5-HT周转率。与MP-3022一样，(S)-WAY 100135拮抗8-OH-DPAT诱导的效应。还已证明(S)-WAY 100135在5-HT1A受体上没有内在活性。所获得的数据表明，与(S)-WAY 100135一样，MP-3022在突触前和突触后5-HT1A受体上表现为功能性拮抗剂。
