Summary
Remoxipride and its active metabolites, the phenolic compounds FLA 797(−) and FLA 908(−) and the catecholic NCQ 436(−) and haloperidol, were examined for their ability to block hypothermia in the rat induced by dopamine (DA) D2 receptor stimulation. In addition, plasma levels of remoxipride and its active metabolites were measured using HPLC methods. Remoxipride (1 μmol/kg), given 30 or 15 min prior to, or 5 and 15 min after, the DA agonists, blocked the hypothermia induced by the DA D2 receptor agonists quinpirole (0.25mg/kg s.c.) and pergolide (0.1 mg/kg s.c). Administration of remoxipride by the i.v. or s.c. routes was more effective than by the i.p. route. FLA 797(−), FLA 908(−), and haloperidol were more effective than remoxipride in preventing the hypothermia caused by quinpirole, while NCQ 436(−) was less effective than remoxipride. The variation in time of remoxipride's action and effectiveness in blocking the induced hypothermia followed the variations in plasma concentrations. The plasma concentrations of the active metabolites were below the limit of determination (<2 nmol/l). Based on estimation of free brain concentrations at effective dose levels together with in vitro affinities for the DA D2 receptor it was concluded that the metabolites FLA 797(−), FLA 908(−), and NCQ 436(−) do not appear to contribute to the antagonism of DA D2 mediated neurotransmission following a low remoxipride dose (1 μmol/kg).
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Ögren, S.Ö., Lundström, J., Nilsson, L.B. et al. Dopamine D2 blocking activity and plasma concentrations of remoxipride and its main metabolites in the rat. J. Neural Transmission 93, 187–203 (1993). https://doi.org/10.1007/BF01244996
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DOI: https://doi.org/10.1007/BF01244996