Remoxipride

Absorption

Remoxipride is approximately 90% bioavailable. In patients with normal creatinine clearance, remoxipride reaches a Cmax of 5.5 ± 1.1 μmol/L, with a Tmax of 0.8 ± 0.2 h, and an AUC of 39 ± 9 μmol*h/L. In patients with moderate renal impairment, remoxipride reaches a Cmax of 7.7 ± 2.7 μmol/L, with a Tmax of 0.9 ± 0.4 h, and an AUC of 63 ± 34 μmol*h/L. In patients with severe renal impairment, remoxipride reaches a Cmax of 9.3 ± 2.3 μmol/L, with a Tmax of 1.4 ± 0.9 h, and an AUC of 123 ± 60 μmol*h/L.

Toxicity

Remoxipride was withdrawn from the market after 8 cases of aplastic anemia were reported. Of those 8 cases, 2 were fatal.

The Uses of Remoxipride

Antipsychotic.

Background

Remoxipride is an atypical antipsychotic agent that is specific for dopamine D2 receptors. It gained approval in the UK in 1989 but was withdrawn in 1993 after it was found to be associated with an increased incidence of aplastic anemia.

Indications

Remoxipride is an atypical antipsychotic once used for the treatment of schizophrenia.

Definition

ChEBI: 3-bromo-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2,6-dimethoxybenzamide is a dimethoxybenzene.

General Description

Remoxipride is a D₂ receptorblocker.It is as effective as haloperidol with fewer EPS andautonomic side effects. Negative symptoms of schizophreniaare diminished. The drug is classed as an atypical antipsychotic.Life-threatening aplastic anemia was reported with itsuse, which prompted its withdrawal from the market.
With respect to the atypical antipsychotics, two eventslong in the past may shed some light on the events of today.
The field of reuptake-inhibiting antidepressants arose whenonly a very small structural change was made in an antipsychoticdrug, and the new activity noted. (The antipsychoticactivity remained.) Therefore, small changes in structurecan produce antipsychotics that are active against depressivesymptoms. Likewise, small changes in structure could provideselectivity among D₂ receptors.

Pharmacokinetics

Remoxipride is a weak selective dopamine D2 receptor antagonist that was once used in the treatment of schizophrenia. It has a moderate therapeutic index and duration of action. Remoxipride was withdrawn due to deaths associated with aplastic anemia.

Metabolism

Remoxipride can be N-dealkylated to FLA 853, oxidized to FLA 850, or N-deethylated to FLA 838. FLA 838 can be oxidized to NCL 118 which is further hydroxylated to NCM 009. FLA 850 can be N-deethylated to NCL 118 or hydroxylated to NCM 001. NCM 001 is further N-deethylated to NCM 009. None of these metabolites have measurable activity on dopamine D2 receptors.