The Effect of Methysergide, Pimozide, and Sodium Valproate on the Diazepam-Stimulated Growth Hormone Secretion in Man

Abstract

Diazepam-induced GH secretion was tested on 28 male volunteers before and after a 3-day treatment with methysergide, pimozide, or sodium valproate. Serum GH, diazepam, and blood glucose levels were determined. Without prior medication, the mean serum GH level increased 336% 1 h after diazepam administration. Treatment with the serotonin antagonist, methysergide, had no effect on the diazepam-stimulated GH secretion, whereas pimozide, the selective dopamine receptor-blocking agent, reduced the GH response to diazepam by 50% (P less than 0.05). Sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, also inhibited diazepam-induced GH secretion; stimulated GH levels were 51% at 30 min (P less than 0.025), 39% at 60 min (P less than 0.025), and 46% at 90 min (P less than 0.025) relative to the stimulated levels without medication. No difference was found in blood glucose or serum diazepam levels after the drug treatments relative to the values obtained under basal conditions. It is suggested that diazepam-induced GH secretion is at least partly mediated via dopaminergic mechanisms. Serotonin does not seem to be involved. It is further proposed that gamma-aminobutyric acid plays an inhibitory role in GH secretion.

Effect of Glucose on Growth Hormone, Prolactin and Thyroid-Stimulating Hormone Response to Diazepam in Normal Subjects

“…The data reported herein confirm previous observations indicating that di azepam can be used as a provocative test for GH release (1,2). This response was suppressed completely when the mean glucose concentration reached 126 mg/ml after glucose load.…”

“…While the effect of diazepam on growth hormone (GH) release in humans has been reported earlier (1,2), its effect on prolactin release (3,4) and thyroid function tests (5-7) is contradictory. A number of studies attempted to associ ate its action with most neurotransmitters (8)(9)(10).…”

Neuroendocrine and Monoaminergic Responses to Acute Administration of Alprazolam in Normal Subjects

“…The effect of alprazolam on GH demonstrated in this study is also consistent with previous findings. It has been shown repeatedly that diazepam [11,12,21] and bromazepam [22] stimulate GH secretion within 1 h of oral adminis tration.…”

“…For alprazolam, it has been suggested that the antipanic mechanism of action may be due, in part, to an interaction between the benzodiazepine re ceptors and the noradrenergic neural system [3] or due to an aIpha-2-agonistic effect [10], Measurements of plasma hormones following a cen trally active pharmacological challenge are commonly used as possible marker for involvement of central neu rotransmitter systems. Benzodiazepines have been shown to consistently raise growth hormone (GH) [11][12][13] and reduce ACTH and cortisol [14. 15].…”

Effects of Sodium Valproate and Diazepam on Beta-Endorphin, Beta-Lipotropin and Cortisol Secretion Induced by Hypoglycemic Stress in Humans

“…Plasma levels of p-endorphin (P-EP), and cortisol were measured as marker of the HPA axis [17,24]. To evaluate the possible acute effect of sodium valproate or diazepam, we used a dose reported to be effective in altering secretion of other pituitary hormones in humans [18,25]. Moreover, because HPA axis response to stress is an important physiological model, we tested the response of plasma P-EP, P-LPH and cortisol on insulin-induced hypoglycemia, following pre treatment with sodium valproate or diazepam.…”