Indantadol, a novel NMDA antagonist and nonselective MAO inhibitor for the potential treatment of neuropathic pain.
Indantadol is an oral and nonselective monoamine oxidase inhibitor and NMDA antagonist that is being developed by Vernalis plc, under license from Chiesi Farmaceutici SpA, for the potential treatment of neuropathic pain. In preclinical studies, indantadol exhibited neuroprotective effects after kainite-induced seizures, and displayed anticonvulsant and antihyperalgesic activity. Indantadol also caused a dose-dependent decrease in exploratory motility. In a human heat-capsaicin-induced pain model, indantadol at a dose of 500 mg effectively reduced the area of secondary hyperalgesia to 67%. Indantadol undergoes extensive liver metabolism, withthe formation of two major metabolites - CHF-3567 and 2-aminoindane. The drug is excreted in urine partially as the parent compound, but mostly as CHF-3567. The tolerability profile of indantadol at single doses up to 600 mg and twice-daily doses up to 400 mg in clinical trials was significantly more favorable than for other NMDA antagonists. Most side effects have been observed to be mild, and include dizziness and asthenia. Indantadol is currently in phase II clinical trials in patients with diabetic peripheral neuropathic pain. Given the results available to date, indantadol may have a role in the treatment of neuropathic pain if the favorable pharmacokinetic profile and efficacy of the drug are maintained in more extensive clinical trials.
Mattia
Consalvo
C
Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, University of Rome La Sapienza, Viale del Policlinico 155, I-00161 Rome, Italy. consalvo.mattia@uniroma1.it
Coluzzi
Flaminia
F
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010146:Pain / Q000188:drug therapy*