Remoxipride

371.275

371.27

0223RD59PE

DTXSID6045668

N - Nervous system

50.8

2.9

Solid

1.292

439.9ºC at 760 mmHg

219.8ºC

1.54

1.27e-01 g/L

3

R36/37/38:Irritating to eyes, respiratory system and skin .

S26-S36-S24/25

Xi

Remoxipride was withdrawn from the market after 8 cases of aplastic anemia were reported.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

Remoxipride is approximately 80% protein bound, mainly to α-1-acid glycoprotein.

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

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 Remoxipride was withdrawn due to deaths associated with aplastic anemia.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)|Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)

Remoxipride is approximately 90% bioavailable. In patients with normal creatinine clearance, remoxipride reaches a C_max of 5.5 ± 1.1 µmol/L, with a T_max of 0.8 ± 0.2 h, and an AUC of 39 ± 9 µmol\*h/L. In patients with moderate renal impairment, remoxipride reaches a C_max of 7.7 ± 2.7 µmol/L, with a T_max of 0.9 ± 0.4 h, and an AUC of 63 ± 34 µmol\*h/L. In patients with severe renal impairment, remoxipride reaches a C_max of 9.3 ± 2.3 µmol/L, with a T_max of 1.4 ± 0.9 h, and an AUC of 123 ± 60 µmol\*h/L.|A dose of remoxipride is 89% recovered in the urine and 7% in the feces. 10-40% of a dose of remoxipride is recovered in the urine as the unchanged parent drug.|The volume of distribution of remoxipride in patients with normal creatinine clearance is 44.3 ± 8.3 L, in patients with moderate renal impairment is 37.4 ± 16.2 L, and in patients with severe renal impairment is 30.2 ± 9.4 L.|The renal clearance of remoxipride in patients with normal creatinine clearance is 23.6 ± 7.0 mL/min, in patients with moderate renal impairment is 9.3 ± 3.8 mL/min, and in patients with severe renal impairment is 3.7 ± 2.9 mL/min. The systemic plasma clearance of remoxipride is 120 mL/min.

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.

The half life of remoxipride in patients with normal creatinine clearance is 5.1 ± 1.6 h, in patients with moderate renal impairment is 6.1 ± 2.6 h, and in patients with severe renal impairment is 9.9 ± 3.8 h.

Remoxipride is an atypical antipsychotic dopamine D₂ antagonist. Chronic use upregulates the expression of D₂ receptors, while downregulating the expression of D₁ and D₅ receptors in the prefrontal cortex. This activity may be related to the antipsychotic activity of remoxipride. Remoxipride displays weaker binding to D₂ dopaminergic receptors that dopamine. This weaker binding is thought to account for the reduced incidence of Parkinsonism. Remoxipride also increases expression of the protein _Fos_ in the nucleus accumbens but not the dorsolateral striatum, which may be responsible for a reduced incidence of extrapyramidal symptoms.

(S)-3-Bromo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,6-dimethoxybenzamide