Cimetidine-Induced Prolactin Release: Possible Involvement of the GABA-Ergic System

Abstract

The mechanism of cimetidine-induced prolactin (PRL) release was studied. Intracarotid (i.a.) administration of 1 mg/kg of impromidine, the most specific H₂ histamine agonist known, did not counteract the cimetidine-induced hypersecretion of PRL. Pre-treatment with benzodiazepines (diazepam or lorazepam, 3 mg/kg/i.a.) completely suppressed it. Administration of γ-aminobutyric acid (GABA 5 mg/kg/i.a.) was also able to prevent it, but to a lesser extent than benzodiazepines. Simultaneous administration of doses of diazepam (1.5 mg/kg/i.a.) and GABA (3 mg/kg/i.a.) ineffective per se markedly blunted the increase of PRL by cimetidine. We conclude that cimetidine does not induce hypersecretion of PRL by its action on histamine H₂ receptors, but through other pharmacological activities of the drug, such as perhaps interaction with the GABA-ergic system in the pituitary.

Efficacy of Multidrug Therapy Combined with Mizoribine in Children with Diffuse IgA Nephropathy in Comparison with Multidrug Therapy without Mizoribine and with Methylprednisolone Pulse Therapy

“…The clinical risk factors for a poor outcome of IgAN have been reported to include renal dysfunction at onset, higher degrees of proteinuria, hypertension, and chronic pathological changes in the kidneys, including glomerular sclerosis, tubular atrophy, and interstitial fibrosis [2,3,4,5,6,7,8,9]. …”

“…IgAN is the most common form of chronic glomerulonephritis worldwide and progresses to end-stage renal failure in up to 30% of the patients [2,3,4]. …”

Effects of quinidine and cimetidine on the methamphetamine level in the rat brain.

“…Thus, the enhancing effect of cimetidine on me thamphetamine stereotypy (2) can be explained by the increased levels of me thamphetamine and amphetamine in the brain as a result of the drug interaction. Further more, cimetidine has been reported to influence not only the activity of the central histaminergic system, but also those of serotonergic, GABAergic systems and dopamine autoreceptors (19)(20)(21). The pos sibility that cimetidine might have affected the stereotypy of methamphetamine via modulating the activity of the above-men tioned neurotransmitter systems may also, in part, need to be considered.…”