Zolmitriptan-induced growth hormone release in humans: mediation by 5-HT1Dreceptors?

Rationale: Effective neuroendocrine probes of 5-HT1B and 5-HT1D receptor fu nction may facilitate investigation of the role of these receptor subtypes in the pathophysiology of depression and the mode of action of antidepressa nt medication. Objective: To investigate the neuroendocrine profile of the 5-HT1B/1D receptor agonist, zolmitriptan, in healthy volunteers. Methods: T welve subjects entered a double-blind, placebo-controlled, cross-over desig n study of zolmitriptan (5 mg orally). Blood samples were taken at 15-min i ntervals for assay of prolactin and growth hormone. A further six healthy m en were recruited to an equivalent study to examine the effect of ketanseri n (a 5-HT receptor antagonist with some preference for 5-HT1D over 5-HT1B r eceptors) on the growth hormone response to zolmitriptan. Results: Zolmitri ptan significantly increased plasma growth hormone but had no effect on pla sma prolactin or oral temperature. The increase in growth hormone produced by zolmitriptan was significantly attenuated by ketanserin. Conclusions: We suggest that the ability of triptans such as zolmitriptan, sumatriptan and rizatriptan to increase plasma growth hormone is mediated by their common agonist activity at postsynaptic 5-HT1D receptors.