Glaum S R, Proudfit H K, Anderson E G
Department of Pharmacology, University of Illinois, College of Medicine, Chicago 60680.
Brain Res. 1990 Feb 26;510(1):12-6. doi: 10.1016/0006-8993(90)90721-m.
The selective 5-HT3 receptor agonist 2-methyl-serotonin (2-Me-5-HT) mimicked the antinociceptive activity of 5-HT when intrathecally administered to rats. Two hundred micrograms (i.t.) doses of these agonists produced similar increases in tail flick latency. However, equal doses of 2-Me-5-HT and 5-HT doubled and tripled, respectively, the mean response latency as measured by the hot plate test. The potent and selective 5-HT3 receptor antagonists ICS 205-930 (3-tropanyl-indole-3-carboxylate) and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) antagonized the antinociceptive effects of both 5-HT and 2-Me-5-HT. However, there were differences in the efficacy of these antagonists. Thus, intrathecal pretreatment with ICS 205-930 (0.05 micrograms) or MDL 72222 (0.1 micrograms) blocked the antinociceptive effects of 5-HT (200 micrograms, i.t.) as measured by the tail flick test, however, higher doses (0.1 and 1.0 micrograms, respectively) were required in the hot plate test. Pretreatment with ICS 205-930 (0.1 microgram) or MDL 72222 (0.1 microgram) blocked the effects of 2-Me-5-HT (200 micrograms, i.t.) in both analgesiometric tests. It is concluded that 5-HT3 receptors are intimately involved in the modulation of spinal nociceptive responses.
鞘内注射选择性5-羟色胺3（5-HT3）受体激动剂2-甲基-5-羟色胺（2-Me-5-HT）时，其可模拟5-羟色胺（5-HT）的抗伤害感受活性。鞘内注射200微克剂量的这些激动剂可使甩尾潜伏期产生相似的增加。然而，通过热板试验测定，相同剂量的2-Me-5-HT和5-HT分别使平均反应潜伏期增加了两倍和三倍。强效且选择性的5-HT3受体拮抗剂ICS 205-930（3-托烷吲哚-3-羧酸酯）和MDL 72222（3-托烷-3,5-二氯苯甲酸酯）可拮抗5-HT和2-Me-5-HT的抗伤害感受作用。然而，这些拮抗剂的效力存在差异。因此，鞘内预先注射ICS 205-930（0.05微克）或MDL 72222（0.1微克）可阻断通过甩尾试验测定的5-HT（20,0微克，鞘内注射）的抗伤害感受作用，然而，在热板试验中则需要更高的剂量（分别为0.1和1.0微克）。预先注射ICS 205-930（0.1微克）或MDL 72222（0.1微克）可在两种镇痛测定试验中阻断2-Me-5-HT（200微克，鞘内注射）的作用。得出的结论是，5-HT3受体密切参与脊髓伤害感受反应的调节。
