ANTINOCICEPTIVE INTERACTION BETWEEN ALPRAZOLAM AND OPIOIDS

Alprazolam is a triazolobenzodiazepine, with a potent anxiolytic actio n and a short half-life. Alprazolam analgesia was measured, using the radiant heat tailfIick assay in mice, which was administered alone or in combination with opioids. Intrathecally administered alprazolam pro duced a dose-response increase in the tailfIick latency with an ED(50) of 34 mu g (19.4-72.5, 95% CL). There were almost no effects after in tracerebroventricular injections. Naloxone almost completely abolished the analgesia response mediated by alprazolam. This sensitivity to na loxone indicates that at least some of the analgesic effects of alpraz olam are mediated by an opioid mechanism of action. When administered together with various antagonists of opioid receptor subtypes, we foun d that the mu antagonists, but not the delta and kappa(1) subtypes inh ibited alprazolam analgesia significantly. Mo effect was found when al prazolam was coadministrated with kappa(3) opioid agonists. In additio n, we found a supra-additivity (synergistic) increase in analgesia whe n alprazolam was given with morphine. Competition binding assays show the highest affinity of alprazolam to the mu(1) subtype. In summary, w e conclude that alprazolam mediates its analgesic effect, most probabl y via an mu opiate mechanism of action. Copyright (C) 1997 Elsevier Sc ience Inc.