''N''-Desmethylclozapine (NDMC), or norclozapine, is a major

active Active may refer to: Music * ''Active'' (album), a 1992 album by Casiopea * Active Records, a record label Ships * ''Active'' (ship), several commercial ships by that name * HMS ''Active'', the name of various ships of the British Royal ...

metabolite of the

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...

drug

clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

. Unlike clozapine, it possesses

intrinsic activity Intrinsic activity (IA) and efficacy refer to the relative ability of a drug- receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its mol ...

at the D₂/ D₃ receptors, and acts as a weak

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

at these sites similarly to

aripiprazole Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...

and bifeprunox. Notably, NDMC has also been shown to act as a potent and efficacious agonist at the M₁ and

δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous lig ...

s, unlike clozapine as well. It was hypothesized that on account of these unique actions, NDMC might underlie the clinical superiority of clozapine over other antipsychotics. However,

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s found NMDC itself ''ineffective'' in the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

. This may be because it possesses relatively low D₂/D₃ occupancy compared to 5-HT₂ (<15% versus 64-79% at a dose of 10–60 mg/kg s.c. in animal studies). Albeit not useful in the treatment of positive symptoms on its own, it cannot be ruled out that NDMC may contribute to the efficacy of clozapine on cognitive and/or negative symptoms.

References

Antipsychotics Chloroarenes Delta-opioid receptor agonists Dibenzodiazepines Mu-opioid receptor agonists Muscarinic agonists Piperazines Human drug metabolites {{Analgesic-stub

See also

References