De Martino Gabriella, La Regina Giuseppe, La Torre Francesco, Cirilli Roberto, Mereghetti Ilario, Cagnotto Alfredo, Artico Marino, Silvestri Romano
Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Roma, Italy.
Farmaco. 2005 Nov-Dec;60(11-12):931-7. doi: 10.1016/j.farmac.2005.07.007. Epub 2005 Oct 11.
The affinities of the enantiomers of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine, 5) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine, 6) were evaluated in receptor binding assays. Compound (+)-(S)-5, the most significant tested enantiomer, showed good affinities for 5-HT1A, 5-HT2A 5-HT2C and alpha2NA receptors, moderate affinities for DA1, DA3r and 5-HT3 receptors and it was devoid of affinity for DA2, alpha(1NA) and muscarinic receptors. Compound (+)-(S)-5 showed an interesting pharmacological profile different from those of the reference compounds mirtazepine, mianserin and 6-methoxymianserin.
在受体结合试验中评估了1,3,4,14b-四氢-2,10-二甲基-2H,10H-吡嗪并[2,1-d]吡咯并[1,2-b][1,2,5]苯并三氮杂卓（10-甲基-10-氮杂阿扎氮卓，5）和2-甲基-1,3,4,14b-四氢-2H-吡嗪并[2,1-d]吡咯并[1,2-b][1,2,5]苯并噻二氮卓10,10-二氧化物（噻阿扎氮卓，6）对映体的亲和力。化合物(+)-(S)-5是测试的最具活性的对映体，对5-HT1A、5-HT2A、5-HT2C和α2NA受体表现出良好的亲和力，对DA1、DA3r和5-HT3受体表现出中等亲和力，对DA2、α(1NA)和毒蕈碱受体没有亲和力。化合物(+)-(S)-5显示出一种有趣的药理学特征，与参考化合物米氮平、米安色林和6-甲氧基米安色林不同。
