Newman-Tancredi A, Verrièle L, Chaput C, Millan M J
Department of Psychopharmacology, Institut de Recherches Servier, Paris, France.
Brain Res Bull. 1996;41(2):93-6.
Desipramine (DMI, 15 mg/kg, s.c.) decreased [3H]CGP-12177-labelled cortical beta-adrenoceptor density (Bmax) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the beta-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of beta-adrenoceptor Bmax (-15%; p < 0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [3H]CGP-12177-labelled beta-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the Bmax of [3H]ketanserin-labelled 5-HT2A receptors on acute treatment. These results show that beta-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.
慢性（14天）给予去甲丙咪嗪（DMI，15毫克/千克，皮下注射）可使[³H]CGP - 12177标记的皮质β - 肾上腺素能受体密度（Bmax）降低30%。然而，即使单剂量（毫克/千克）的DMI（15）或β - 肾上腺素能受体激动剂克伦特罗（20）也可迅速（24小时）且显著降低β - 肾上腺素能受体Bmax（-15%；p < 0.01）。急性给予阿米替林（10）、氯吉兰（1）、氟西汀（10）、诺米芬辛（10）或马普替林（20）对[³H]CGP - 12177标记的β - 肾上腺素能受体无显著影响，这表明快速下调可能并非抗抑郁药的普遍特性。急性治疗时，这些抗抑郁药均未改变[³H]酮色林标记的5 - HT₂A受体的Bmax。这些结果表明，克伦特罗和DMI引起的β - 肾上腺素能受体下调并不依赖于慢性治疗，因此可能与临床上抗抑郁药治疗效果的逐渐显现相关性较差。
