A long‐term study of remoxipride in chronic schizophrenic patients

Abstract

The purpose of this study was to assess the tolerability and efficacy of 150-600 mg remoxipride (predominantly a DA2 receptor antagonist) in an open long-term (1 year) multicentre trial in chronic schizophrenic patients. The mean duration of illness before entering the study was 21 years and the pre-study neuroleptic dosage in chlorpromazine equivalents was 930 mg/day. The clinical efficacy was measured with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. The adverse events were recorded by a 26-item Adverse Symptom Checklist and by the Abnormal Involuntary Movements Scale. Forty-five patients were included in the study. The mean daily dose of remoxipride during the last week of treatment was 378 mg. Eighty percent (36 patients) withdrew prematurely (< 1 year). The main reasons for withdrawal were: ineffectiveness (n = 15), treatment refusal (n = 12) and adverse events (n = 8). The most frequently reported adverse events were insomnia (n = 20) and tiredness (n = 7), whereas only a few (n = 6) extrapyramidal symptoms were reported. There was no relationship between remoxipride plasma concentration and clinical efficacy nor was any relationship found between the ratio of pretrial chlorpromazine equivalent to last remoxipride dose and the therapeutic effect. Remoxipride alone seemed to have an insufficient neuroleptic efficacy in these chronic and treatment-resistant schizophrenic patients but was well tolerated.

A Review of the Discovery, Pharmacological Characterization, and Behavioral Effects of the Dopamine D2‐Like Receptor Antagonist Eticlopride

“…Using sulpiride as a starting model, chemists at Astra Pharmaceuticals manipulated the aromatic substituents to develop compounds that were more potent in animal models of psychosis and were more selective for DA D2‐like receptors [19,21,24]. One of the first major successes in this focused SAR development of ligands was remoxipride, an effective antipsychotic agent with high affinity for DA D2‐like receptors that was introduced into the market in 1992 [25–29]; however, despite low occurrence of EPS, it was quickly withdrawn from clinical use due to an association with a rare blood dyscrasia [24,29,30]. Soon after remoxipride, the binding affinity for DA D2‐like receptors was again increased with the development of raclopride, a 3,5‐dichloro analogue of sulpiride with halogens in the meta position of the aromatic ring [21].…”

New Insights into the Biology of Schizophrenia through the Mechanism of Action of Clozapine

“…For instance, the observation that remoxipride, a D2 receptor antagonist with very little affinity for 04 receptors, exerts antipsychotic activity comparable to conventional neuroleptics without producing strong extrapyramidal side-effects (Kohler et al 1990;Lewander et al 1990;Kane 1993), suggests that D4 blockade is not a prerequisite for atypical antipsychotic activity. However, remoxipride has been reported not to be effective in chronic or treatment-resistant patients (Vartiainen et al 1993). Thus, it cannot be excluded that a preferential 04 receptor blocking activity of clozapine is in part responsible for its activity in treatment-resistant patients.…”

Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors

“…82 Such treatment-resistant patients, however, also respond (sometimes dramatically) to remoxipride, [83][84][85] which is extremely selective for D2 (Table 1). In fact, remoxipride clinically improves at least 30% of treatmentresistant schizophrenia patients.…”