Syvälahti E K, Laurén L, Markkanen J, Kunelius R
Pharmacol Toxicol. 1987 Jan;60(1):66-9. doi: 10.1111/j.1600-0773.1987.tb01722.x.
It is generally accepted that there are at least three different subtypes of muscarinic cholinoceptors, pirenzepine being considered a selective M1 antagonist. In the present study, a number of different types of psychotropic drugs have been compared with pirenzepine and atropine as reference antimuscarinic drugs regarding their affinities for rat brain muscarinic cholinoceptors with the help of in vitro receptor binding studies. The most potent drugs, inhibiting 3H-1-quinuclidinyl benzilate (3H-QNB) binding at subnanomolar concentrations, were the antimuscarinic drugs scopolamine and atropine. Biperiden, promethazine, pirenzepine and some tricyclic antidepressants (amitriptyline, doxepin) were the next potent drugs, with IC50-values between 8.4 nM and 190 nM. The inhibition curves were steep and parallel giving Hill coefficients close to unity in all but two drugs studied. These exceptions were biperiden and pirenzepine both with Hill coefficients about 0.55. Thus, in addition to pirenzepine also biperiden seems to bind to the M1 receptor selectively. Additional receptor and functional studies are warranted to further elucidate the possible similarities of these two drugs.
一般认为，毒蕈碱型胆碱能受体至少有三种不同的亚型，哌仑西平被认为是一种选择性M1拮抗剂。在本研究中，借助体外受体结合研究，将多种不同类型的精神药物与作为参考抗毒蕈碱药物的哌仑西平和阿托品进行了比较，比较它们对大鼠脑毒蕈碱型胆碱能受体的亲和力。抑制3H-1-喹核醇基苯甲酸酯（3H-QNB）在亚纳摩尔浓度下结合的最有效药物是抗毒蕈碱药物东莨菪碱和阿托品。比哌立登、异丙嗪、哌仑西平和一些三环类抗抑郁药（阿米替林、多塞平）是次有效药物，IC50值在8.4 nM至190 nM之间。除两种研究药物外，所有药物的抑制曲线都很陡峭且平行，希尔系数接近1。这两个例外是比哌立登和哌仑西平，它们的希尔系数均约为0.55。因此，除哌仑西平外，比哌立登似乎也选择性地与M1受体结合。有必要进行额外的受体和功能研究，以进一步阐明这两种药物可能的相似之处。
