Tonini M, Candura S M, Onori L, Coccini T, Manzo L, Rizzi C A
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Life Sci. 1992;50(21):PL173-8. doi: 10.1016/0024-3205(92)90453-v.
The effect of 5-hydroxytryptamine (5-HT), BIMU 8 (endo-N-(8-methyl-8-azabicyclo [3.2.1.] oct-3-yl)-2,3-dihydro-3-(1-methyl)ethyl-2-oxo-1H-benzimidazole-1- carboxamide hydrochloride) and cisapride was studied on the electrically-induced neurogenic cholinergic twitch contractions in the guinea pig ileum circular muscle. These compounds caused a concentration-dependent increase in the amplitude of submaximal twitch contractions with the following rank order of potency: 5-HT greater than BIMU 8 = cisapride. The effect of 5-HT was competitively antagonized by tropisetron (ICS 205-930) (apparent pA2 value: 6.4), suggesting an interaction at 5-hydroxytryptamine4 (5-HT4) receptors. The novel benzimidazolone derivative DAU 6285 (endo-6-methoxy-8-methyl-8-azabicyclo [3.2.1.] oct-3-yl-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylate hydrochloride), antagonized the effect of 5-HT, BIMU 8 and cisapride with apparent pA2 values in the range 7.1-7.3. Our findings demonstrate that cholinergic neurones innervating the circular coat are endowed with excitatory 5-HT4 receptors. DAU 6285 is approximately 5-9-fold more potent than tropisetron as antagonist at these receptors.
研究了5-羟色胺（5-HT）、BIMU 8（内-N-(8-甲基-8-氮杂双环[3.2.1]辛-3-基)-2,3-二氢-3-(1-甲基)乙基-2-氧代-1H-苯并咪唑-1-羧酰胺盐酸盐）和西沙必利对豚鼠回肠环行肌电诱导神经源性胆碱能抽搐收缩的影响。这些化合物使次最大抽搐收缩的幅度呈浓度依赖性增加，其效力顺序如下：5-HT＞BIMU 8 =西沙必利。托烷司琼（ICS 205-930）竞争性拮抗5-HT的作用（表观pA2值：6.4），提示在5-羟色胺4（5-HT4）受体处存在相互作用。新型苯并咪唑酮衍生物DAU 6285（内-6-甲氧基-8-甲基-8-氮杂双环[3.2.1]辛-3-基-2,3-二氢-2-氧代-1H-苯并咪唑-1-羧酸盐盐酸盐）拮抗5-HT、BIMU 8和西沙必利的作用，表观pA2值在7.1 - 7.3范围内。我们的研究结果表明，支配环行肌层的胆碱能神经元具有兴奋性5-HT4受体。在这些受体上，DAU 6285作为拮抗剂的效力比托烷司琼强约5 - 9倍。
