Groenink L, Van der Gugten J, Mos J, Maes R A, Olivier B
Department of Psychopharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Netherlands.
Eur J Pharmacol. 1995 Jan 16;272(2-3):177-83. doi: 10.1016/0014-2999(94)00645-n.
We tried to antagonize the endocrine and behavioural changes induced by the selective 5-HT1A receptor agonist, flesinoxan, with the putative 5-HT1A receptor antagonist, (S)-UH301 ((S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin). The interaction of (S)-UH301 (3 and 10 mg/kg s.c.) with flesinoxan (3 mg/kg s.c.) showed no antagonistic effects of (S)-UH301 on flesinoxan-induced corticosterone secretion. In fact, like flesinoxan (1 and 3 mg/kg s.c.), (S)-UH301 (3 and 10 mg/kg s.c.) itself dose dependently increased plasma corticosterone levels. Unlike flesinoxan, (S)-UH301 did not induce hyperglycemia, lower lip retraction and flat body posture. Moreover, flesinoxan-induced hyperglycemia and behavioural changes were effectively antagonized by (S)-UH301, showing potent 5-HT1A receptor antagonistic effects of (S)-UH301. Therefore we conclude that (S)-UH301 is a potent 5-HT1A receptor antagonist and that the (S)-UH301-induced corticosterone secretion is mediated by a non-5-HT1A receptor mechanism.
我们试图用假定的5-HT1A受体拮抗剂（S）-UH301（（S）-5-氟-8-羟基-2-（二正丙基氨基）四氢萘）来对抗选择性5-HT1A受体激动剂氟西汀诱导的内分泌和行为变化。（S）-UH301（3和10毫克/千克，皮下注射）与氟西汀（3毫克/千克，皮下注射）的相互作用表明，（S）-UH301对氟西汀诱导的皮质酮分泌没有拮抗作用。事实上，与氟西汀（1和3毫克/千克，皮下注射）一样，（S）-UH301（3和10毫克/千克，皮下注射）本身也剂量依赖性地增加血浆皮质酮水平。与氟西汀不同，（S）-UH301不会诱导高血糖、下唇回缩和平躺姿势。此外，（S）-UH301有效对抗了氟西汀诱导的高血糖和行为变化，显示出（S）-UH301具有强大的5-HT1A受体拮抗作用。因此，我们得出结论，（S）-UH301是一种有效的5-HT1A受体拮抗剂，并且（S）-UH301诱导的皮质酮分泌是由非5-HT1A受体机制介导的。
