The effects of methaqualone on pituitary-adrenocortical activity in mice

Methaqualone produces a dose- and time-dependent increase in plasma corticosterone concentration in mice. Acute studies showed that this effect is largely independent of methaqualone-induced hypothermia but can be blocked by pretreatment with dexamethasone, thus demonstrating that the adrenal cortex is not being directly stimulated. It is not clear whether the pituitary-adrenal activation is primarily caused by methaqualone itself or by a hepatic metabolite(s) since pretreatment with SKF 525-A failed either to potentiate or block the effect. Studies employing chronic methaqualone administration provided evidence for a rapid development of tolerance to the pituitary-adrenal effect of the drug. Dose- and time-response studies demonstrated a parallel between plasma concentrations of methaqualone and the stimulation of pituitary-adrenal activity. Furthermore, drug concentrations 1 h following methaqualone administration were diminished in chronically pretreated animals was compared to those previously untreated, suggesting that an altered metabolism of methaqualone may be responsible for the development of tolerance.