The antinociceptive effect of reversible monoamine oxidase-A inhibitors in a mouse neuropathic pain model.

Neuropathic pain is a debilitating condition that is often resistant to common analgesics, such as opioids, but is sensitive to some antidepressants, an effect that seems to be mediated by spinal cord 5-HT3 receptors. Because the analgesic potential of monoamine oxidase-A (MAO-A) inhibitors is understudied, we evaluated the potential antinociceptive effect of the reversible MAO-A inhibitors moclobemide and 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in a mouse neuropathic pain model induced by chronic constriction injury (CCI) of the sciatic nerve. Neuropathic mice showed a decreased mechanical paw withdrawal threshold (PWT) 7 days after lesion compared with the baseline PWT, characterizing the development of hyperalgesia. Moclobemide (100-300 µmol/kg, s.c.) and 2-DMPI (30-300 µmol/kg, s.c.) treatments were able to reverse the CCI-induced hyperalgesia, with 50% inhibitory dose (ID50) values of 39 (18-84) and 11 (4-33) µmol/kg, and maximum inhibition (Imax) values of 88±14 and 98±15%, respectively, at the 300 µmol/kg dose. In addition, we observed a significant increase in the MAO-A activity in the lumbar spinal cord of CCI-submitted mice compared with sham-operated animals. Furthermore, the antihyperalgesic effects of both 2-DMPI and moclobemide were largely reversed by intrathecal injection of the 5-HT3 receptor antagonist ondansetron (10 µg/site). These results suggest a possible involvement of MAO-A in the mechanisms of neuropathic pain and a potential utility of the reversible inhibitors of MAO-A in the development of new therapeutic approaches to treat it.

A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder.

The authors compared the outcomes of 35 outpatients with dysthymic disorder randomized to receive either treatment with moclobemide and interpersonal therapy (IPT) or moclobemide and routine clinical management. Diagnosis was based on the ICD-10 symptom checklist. Patients were evaluated by trained raters using the 17-item Hamilton Rating Scale for Depression (Ham-D), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Functioning, and Quality of Life and Satisfaction Questionnaire at baseline, 12, 24, and 48 weeks. Patients in both treatment groups showed statistically significant improvement in all measures across time. There was a nonsignificant trend toward lower scores on Ham-D and MADRS for patients in the moclobemide plus IPT group. Longer, better-powered trials should be carried out to study the efficacy of IPT plus antidepressant medication in the treatment of dysthymic disorder.