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.
D000302:Adrenal Cortex / Q000187:drug effects*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D008702:Methaqualone / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010902:Pituitary Gland / Q000187:drug effects*; D011335:Proadifen / Q000494:pharmacology; D013997:Time Factors
D003907:Dexamethasone; D008702:Methaqualone; D011335:Proadifen; D003345:Corticosterone