Johansson C E, Meyerson B J, Hacksell U
Department of Medical Pharmacology, Uppsala University, Sweden.
Eur J Pharmacol. 1991 Sep 4;202(1):81-7. doi: 10.1016/0014-2999(91)90256-p.
The 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) facilitates male rat copulatory behaviour but inhibits female rat copulatory behaviour. The effect of the novel 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [S)-UH-301) on these 8-OH-DPAT-induced responses was tested. 8-OH-DPAT was given s.c. in a dose of 0.176 mumol/kg (50 micrograms/kg). The doses of (S)-UH-301 given s.c. were 1.76 mumol/kg (0.53 mg/kg) and 5.28 mumol/kg (1.60 mg/kg). The administration of (S)-UH-301 10 min before 8-OH-DPAT antagonized the 8-OH-DPAT-induced effects on both male and female rat copulatory behaviour. The results presented strongly support the classification of (S)-UH-301 as a 5-HT1A receptor antagonist. In addition, the effect of the enantiomer of (S)-UH-301, (R)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [R)-UH-301), on male rat copulatory behaviour was tested. This enantiomer was found to facilitate male rat copulatory behaviour in a 8-OH-DPAT-like manner, supporting a 5-HT1A agonistic action of (R)-UH-301.
5-羟色胺1A受体激动剂8-羟基-2-（二丙基氨基）四氢萘（8-OH-DPAT）可促进雄性大鼠的交配行为，但抑制雌性大鼠的交配行为。本研究测试了新型5-羟色胺1A受体拮抗剂（S）-5-氟-8-羟基-2-（二丙基氨基）四氢萘[S）-UH-301]对这些8-OH-DPAT诱导反应的影响。8-OH-DPAT以0.176 μmol/kg（50 μg/kg）的剂量皮下注射。（S）-UH-301皮下注射的剂量分别为1.76 μmol/kg（0.53 mg/kg）和5.28 μmol/kg（1.60 mg/kg）。在8-OH-DPAT注射前10分钟给予（S）-UH-301，可拮抗8-OH-DPAT对雄性和雌性大鼠交配行为的诱导作用。研究结果有力支持将（S）-UH-301归类为5-羟色胺1A受体拮抗剂。此外，还测试了（S）-UH-301的对映体（R）-5-氟-8-羟基-2-（二丙基氨基）四氢萘[R）-UH-301]对雄性大鼠交配行为的影响。发现该对映体以类似8-OH-DPAT的方式促进雄性大鼠的交配行为，支持（R）-UH-301具有5-羟色胺1A激动作用。
