DISTINCT MECHANISM FOR ANTIDEPRESSANT ACTIVITY BY BLOCKADE OF CENTRALSUBSTANCE-P RECEPTORS

The Localization of substance P in brain regions that coordinate stres s responses and receive convergent monoaminergic innervation suggested that: substance P antagonists might have psychotherapeutic properties . Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pig s. In a placebo-controlled trial in patients with moderate to severe m ajor depression, robust antidepressant effects of the substance P anta gonist MK-869 were consistently observed, in preclinical studies, subs tance P antagonists did not: interact with monoamine systems in the ma nner seen with established antidepressant drugs. These findings sugges t that substance P may play an important role in psychiatric disorders .