ISSN:
1435-1463
Keywords:
Bar test
;
catalepsy
;
remoxipride
;
phenolic metabolites
;
haloperidol
;
plasma
;
brain
;
kinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The cataleptic effect of remoxipride was examined in the horizontal bar test after i.v.,i.p. and s.c. administration to male rats. Remoxipride induced immediate catalepsy after high i.v. doses (ED50=49 μmol/kg) while peak effects were seen 60–90 min after i.p. administration (ED50=38 μmol/kg). Following s.c. administration remoxipride failed to produce a statistically significant catalepsy in the 20–100 μmol/kg dose range (ED50 〉 100 μmol/kg). In contrast, haloperidol was found to be more effective in inducing catalepsy after i.v. (ED50=0.4 μmol/kg) than after i.p. or s.c. administration (ED50=0.9 μmol/ kg). The atypical antipsychotic profile of remoxipride was more pronounced when the compound was given i.v. or s.c. as compared with the i.p. route. Plasma and brain (striatum and nucleus accumbens) concentrations of remoxipride and its active phenolic metabolites FLA 797(−) and FLA 908(−) were measured by high performance liquid chromatography. The 40 μmol/kg dose of remoxipride resulted in plasma and brain concentrations of remoxipride which were 300–1000-fold higher (depending on the route of administration) than the most potent of the phenolic metabolites, e.g., FLA 797(−). The plasma and brain concentrations of remoxipride and its phenolic metabolites were related to DA D2 receptor blocking potency and to the temporal course and effectiveness to induce catalepsy. This analysis suggested that the unbound concentrations of the phenolic metabolites were too low to play a major role in the DA blocking action of remoxipride. However, FLA 797(−) may contribute marginally to the cataleptic effects following high (i.p.) doses of remoxipride.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01277025
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