Skarsfeldt T, Larsen J J
Department of Pharmacology and Toxicology, H. LUNDBECK A/S, Copenhagen-Valby, Denmark.
Eur J Pharmacol. 1988 Apr 13;148(3):389-95. doi: 10.1016/0014-2999(88)90117-3.
The selective dopamine D-1 receptor antagonist SCH 23390 has been tested in vitro in the rat fundus model and in vivo in the electrically stimulated flexor reflex model. In the fundus model, SCH 23390 showed a potent agonistic activity compared to that of different 5-HT receptor agonists. Pindolol, 1-propranolol and pirenperone showed no or only weak inhibition of the SCH 23390-induced contractions in the fundus strip whereas methysergide was a potent inhibitor. The 5-HT3 receptor antagonist ICS 205-930 did not induce an inhibitory effect. In the electrically stimulated flexor reflex model in pithed rats, SCH 23390 induced a marked increase of the reflex. This increase was slightly inhibited by a mixed dopamine (DA) D-1/D-2 antagonist cis(Z)-flupentixol and by a specific DA D-2 antagonist YM 09151-2. Different reference antagonists: bicuculline (GABAergic), propranolol (beta-adrenergic), scopolamine (muscarinic), yohimbine (alpha 2-adrenergic), prazosin (alpha 1-adrenergic) were all without an antagonist effect on the SCH 23390-induced increase of the flexor reflex. Ketanserin, a selective 5-HT2 receptor antagonist, showed a weak and short-lasting inhibition of the SCH 23390 effect in high doses, whereas ritanserin showed only 35% inhibition of the SCH 23390-induced flexor reflex at a dose of 1.3 mumol/kg i.v. The mixed 5-HT1/5-HT2 antagonists methiothepin and metergoline showed a marked inhibitory effect at 2.6 mumol/kg i.v. and 3.1 mumol/kg i.v., respectively (1.3 mg/kg i.v.). These findings suggest that SCH 23390 might possess 5-HT1 receptor agonist activity.
选择性多巴胺D-1受体拮抗剂SCH 23390已在大鼠胃底模型中进行体外测试，并在电刺激屈肌反射模型中进行体内测试。在胃底模型中，与不同的5-羟色胺（5-HT）受体激动剂相比，SCH 23390显示出强效激动活性。吲哚洛尔、普萘洛尔和哌仑西平对胃底条带中SCH 23390诱导的收缩无抑制作用或仅有微弱抑制作用，而麦角新碱是一种强效抑制剂。5-HT3受体拮抗剂ICS 205-930未产生抑制作用。在脊髓切断大鼠的电刺激屈肌反射模型中，SCH 23390使反射明显增强。这种增强作用被多巴胺（DA）D-1/D-2混合拮抗剂顺式（Z）-氟哌噻吨和特异性DA D-2拮抗剂YM 09151-2轻微抑制。不同的参考拮抗剂：荷包牡丹碱（GABA能）、普萘洛尔（β-肾上腺素能）、东莨菪碱（毒蕈碱能）、育亨宾（α2-肾上腺素能）、哌唑嗪（α1-肾上腺素能）对SCH 23390诱导的屈肌反射增强均无拮抗作用。选择性5-HT2受体拮抗剂酮色林在高剂量时对SCH 23390的作用有微弱且持续时间短的抑制作用，而利坦色林在静脉注射剂量为1.3 μmol/kg时仅对SCH 23390诱导的屈肌反射有35%的抑制作用。5-HT1/5-HT2混合拮抗剂甲硫噻平及美替拉酮在静脉注射剂量分别为2.6 μmol/kg和3.1 μmol/kg（1.3 mg/kg静脉注射）时显示出明显的抑制作用。这些发现提示SCH 23390可能具有5-HT1受体激动剂活性。
