Chiral resolution and binding study 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) 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)

Farmaco (Societa chimica italiana : 1989) Pub Date : 2005-11-01 DOI:10.1016/j.farmac.2005.07.007

Gabriella De Martino , Giuseppe La Regina , Francesco La Torre , Roberto Cirilli , Ilario Mereghetti , Alfredo Cagnotto , Marino Artico , Romano Silvestri

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引用次数: 3

Abstract

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-HT_1A, 5-HT_2A 5-HT_2C and α_2NA receptors, moderate affinities for DA₁, DA_3r and 5-HT₃ receptors and it was devoid of affinity for DA₂, α_1NA and muscarinic receptors. Compound (+)-(S)-5 showed an interesting pharmacological profile different from those of the reference compounds mirtazepine, mianserin and 6-methoxymianserin.

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1,3,4,14b-四氢-2,10-二甲基- 2h, 10h -吡嗪基[2,1-d]吡咯基[1,2-b][1,2,5]苯并三氮卓(10-甲基-10-氮唑他平)和2-甲基-1,3,4,14b-四氢- 2h -吡嗪基[2,1-d]吡咯基[1,2-b][1,2,5]苯并噻二氮卓- 10,10-二氮卓(硫唑他平)的手性拆分和结合研究

对1,3,4,14b-四氢-2,10-二甲基- 2h, 10h -吡嗪基[2,1-d]吡咯基[1,2-b][1,2,5]苯并三氮平(10-甲基-10-氮唑他平，5)和2-甲基-1,3,4,14b-四氢- 2h -吡嗪基[2,1-d]吡咯基[1,2-b][1,2,5]苯并噻唑二氮平，10,10-二氧化(硫唑他平，6)的对映体进行了受体结合测定。化合物(+)-(S)-5对5-HT1A、5-HT2A、5-HT2C和α2NA受体具有良好的亲和性，对DA1、DA3r和5-HT3受体具有中等的亲和性，对DA2、α1NA和毒蕈碱受体无亲和性。化合物(+)-(S)-5表现出与米他西平、米安色林和6-甲氧基米安色林不同的药理特征。

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Farmaco (Societa chimica italiana : 1989)

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