Hjorth S, Sharp T, Hacksell U
MRC Unit, Radcliffe Infirmary, Oxford, England.
Eur J Pharmacol. 1989 Nov 7;170(3):269-74. doi: 10.1016/0014-2999(89)90549-9.
The present study assessed the pharmacological activity of the stereoisomers of the novel 8-OH-DPAT analogue cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin, ALK-3, at postsynaptic 5-HT1A receptors involved in 5-HT-mediated behaviour. Reserpine-pretreated rats were injected with (+)8-OH-DPAT (0.03-1.0 mg/kg s.c.), (+)ALK-3 (0.3-10.0 mg/kg s.c.) or (-)ALK-3 (3.0-10.0 mg/kg s.c.), and components of the '5-HT behavioural syndrome' were scored. (+8-OH-DPAT dose dependently elicited forepaw treading, flattened body posture and hindlimb abduction. In this respect, (+)ALK-3 was significantly less efficacious although its behavioural action was prevented by pindolol (8 mg/kg s.c.), indicating that it was 5-HT1A receptor mediated. Following pretreatment, (+)ALK-3 dose dependently, but partially, attenuated the effect of (+)8-OH-DPAT. (-)ALK-3 did not elicit 5-HT behaviours per se, and only very weakly antagonized the behavioural actions of (+)8-OH-DPAT at the highest dose tried. Our data indicate that the (+) enantiomer of ALK-3 is a partial but stereoselective agonist at postsynaptic 5-HT1A receptors.
本研究评估了新型8-OH-DPAT类似物顺式-8-羟基-1-甲基-2-(二正丙基氨基)四氢萘（ALK-3）的立体异构体在参与5-羟色胺（5-HT）介导行为的突触后5-HT1A受体上的药理活性。对利血平预处理的大鼠皮下注射(+)8-OH-DPAT（0.03 - 1.0毫克/千克）、(+)ALK-3（0.3 - 10.0毫克/千克）或(-)ALK-3（3.0 - 10.0毫克/千克），并对“5-HT行为综合征”的各项指标进行评分。(+)8-OH-DPAT剂量依赖性地引发前爪踩踏、身体姿势扁平及后肢外展。在这方面，(+)ALK-3的效力明显较低，尽管其行为作用可被吲哚洛尔（8毫克/千克，皮下注射）阻断，表明这是由5-HT1A受体介导的。预处理后，(+)ALK-3剂量依赖性但部分地减弱了(+)8-OH-DPAT的作用。(-)ALK-3本身不会引发5-HT行为，且在尝试的最高剂量下仅非常微弱地拮抗(+)8-OH-DPAT的行为作用。我们的数据表明，ALK-3的(+)对映体是突触后5-HT1A受体的部分但具有立体选择性的激动剂。
