Does alprazolam, in contrast to diazepam, activate alpha 2-adrenoceptors involved in the regulation of rat growth hormone secretion?

The conventional benzodiazepine diazepam and the novel triazolobenzodiazepine alprazolam were compared with respect to effects on growth hormone (GH) release in reserpine pretreated rats. The reserpine pretreatment was undertaken to eliminate brain monoaminergic influence on GH secretion, hence obtaining a low GH baseline from which a drug induced increase could be easily detected. Previous studies have indicated that activation of brain alpha 2-adrenoceptors is an indispensable prerequisite for GH release induced by other agents such as serotonin and opiate receptor agonists. In line with these findings, diazepam was found to induce GH release in reserpine pretreated rats only when the alpha 2-receptor agonist clonidine was simultaneously administered. In contrast, alprazolam caused a dose-dependent increase in plasma GH when given alone to reserpine pretreated rats. This effect of alprazolam was effectively antagonized by either of the two selective alpha 2-receptor antagonists yohimbine or idazoxane. The data indicate that alprazolam, but not diazepam, activates brain alpha 2-adrenoceptors involved in rat GH regulation. The possibility that an alpha 2-agonistic profile of alprazolam may contribute to the suggested effectiveness of the drug in the treatment of panic disorder is discussed.