Naloxazone lacks therapeutic effects in endotoxic shock yet blocks the effects of naloxone.

Cardiovascular effects of the high affinity, irreversible opiate antagonist, naloxazone, were investigated in conscious rats subjected to endotoxic shock. Unlike other less selective opiate antagonists such as naloxone, naloxazone failed to block or reverse the hemodynamic effects of endotoxemia. However, naloxazone pretreatment prevented the usual therapeutic effects of naloxone in endotoxic shock. Results indicate that high affinity (mu 1-site) opiate binding is not involved in the pathophysiological actions of endogenous opiates in shock, and suggest that interactions among opioid receptor subtypes may occur in vivo.