Pharmacology of N-desmethylclozapine.
Currently available treatments for schizophrenia have limited efficacy and are generally poorly tolerated. However, among these antipsychotic agents, clozapine stands apart in having generally superior motoric tolerability and efficacy. One intriguing possibility, based on clinical correlations, receptor activity profiles and studies with animal models predictive of antipsychotic or cognitive action is that the activity of N-desmethylclozapine (NDMC), a major metabolite of clozapine, may, at least in part, underlie the unique efficacy of clozapine. In this review we compare the pharmacological properties of NDMC to those of clozapine and consider how they may contribute to the overall clinical properties of clozapine. We also consider whether NDMC, in its own right, might be a superior antipsychotic drug.
Lameh
Jelveh
J
ACADIA Pharmaceuticals Inc, San Diego, California, USA. jlameh@acadia-pharm.com
Burstein
Ethan S
ES
Taylor
Eve
E
Weiner
David M
DM
Vanover
Kimberly E
KE
Bonhaus
Douglas W
DW
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003024:Clozapine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; C058272:norclozapine; D003024:Clozapine