Interaction between the tetracyclic antidepressant mianserin HCl and opioid receptors

The antinociceptive effects of the tetracyclic antidepressant mianserin and its interaction with various opioid receptor subtypes was evaluated. Mice were tested with a hotplate analgesia meter. Mianserin elicited an antinociceptive effect in a dose-dependent manner following doses from 1-25 mg/kg. As the mianserin dose increased beyond 30 mg/kg, latencies returned to baseline, yielding a biphasic effect. This effect of mianserin was antagonized by naloxone (P<0.005), implying a possible opioid mechanism of action involved in the mianserin induced antinociceptive effect. When administered with various opioid antagonists, the sensitivity of mianserin to selective opioid antagonists was found significant for μ and κ1 opioid receptor subtypes (P<0.005), but not for δ-receptor. At the next stage mianserin was administered together with various agonists of opioid receptors. When administered together with opiates, mianserin significantly potentiates analgesia at the μ, κ1 and κ3 opioid receptor subtype (P<0.005) and to a lesser extent, at the δ opioid receptors. These results suggest a potential use of mianserin in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mianserin when prescribed for pain. Copyright (C) 1998 Elsevier Science B.V./ECNP.