Effects of prolonged administration of milnacipran, a new antidepressant, on receptors and monoamine uptake in the brain of the rat.

摘要: Abstract Most antidepressants produce changes in monoamine receptors brain after chronic administration animals. The most commonly described alterations are a decreased density and function of β-adrenergic have been postulated to be the mechanisms by which exert their therapeutic effect. Milnacipran (previous name midalcipran) is new, clinically-effective antidepressant, inhibits uptake both serotonin noradrenaline but has no affinity for any pre- or postsynaptic receptor studied. When given either orally at 7.5 mg/kg twice daily 3 days, 30 once weeks, osmotic mini-pump mg/kg/day 27 drinking water approximately 15 6 weeks washout period 24 hr, milnacipran produced down-regulation β-adrenoceptors. In addition, there were α 1 - 2 -adrenoceptors, 5-HT benzodiazepine binding sites. Moreover, accumulation unmodified. potency inhibit vitro cortex was not altered treated rats, compared control Thus, spite its action on noradrenaline, appears without long-term β-adrenoceptors other studied, suggesting that, least this these modifications essential clinical activity.