Abstract
The tolerability and pharmacokinetics of remoxipride were studied in 18 healthy normal male volunteers. Increasing oral doses of 0.5–100 mg were given to eight male volunteers in one study (study I). In addition, an intravenous (IV) infusion of 20 mg remoxipride and a 20 mg oral dose were given in an open crossover study to ten males (study II). Remoxipride was well tolerated with respect to cardiovascular effects, clinical chemistry, body temperature and adverse effects in all subjects. Following IV administration, remoxipride plasma concentrations declined exponentially in five subjects and biexponentially in the remaining five. The mean apparent volume of distribution was 0.5 1/kg (SD=0.10) and the mean half-life 4.1 h (range 2.6–6.6). The recovery of unchanged remoxipride in urine was 10–36%, and the mean renal clearance was 32 ml/min (SD=13). Remoxipride was a low clearance drug with a total plasma clearance of about 120 ml/min (SD=41). The mean oral bioavailability was 96%. There was a linear relationship between the peak plasma concentration as well as the area under the concentration versus time curve and the administered dose. A transient increase in plasma prolactin concentrations occurred but there were no effects on plasma growth hormone levels.
Similar content being viewed by others
References
Alexander CS, Nino A (1969) Cardiovascular complications in young patients taking psychotropic drugs. Am Heart J 78:757–769
Andersson BG, Reher D, Cooper TB (1981) Prolonged adverse effects of haloperidol in normal subjects. N Engl Med 305:643–644
Axelsson R, Mårtensson E (1980) Side effects of thioridazine and their relationship with the serum concentrations of the drug and its main metabolites. Curr Ther Res 28:463–489
Baldessarini RJ (1985) Drugs used in the treatment of psychosis. In: Goodman-Gilman A, Goodmann LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics, 7th edn. Macmillan, New York, pp 391–412
Collier PS, Riegelman S (1983) Estimation of absolute bioavailability assuming steady state apparent volume of distribution remains constant. J Pharmacokinet Biopharm 10:135–146
Farde L, Grind MI, Nilsson M-I, Ogenstad S, Sedwall G (1988) Remoxipride — a new potential antipsychotic drug. Pharmacological effects and pharmacokinetics following repeated oral administration in male volunteers. Psychopharmacology 95:157–161
Florvall L, Persson ML, Ögren SO (1983) Potential neuroleptic agents 2. Synthesis and dopamine blocking activity of some new 2,6-dimethoxybenzamide dervatives. Acta Pharm Suec 20:365
Forsman A, Öhman R (1976) Pharmacokinetic studies on haloperidol in man. Curr Ther Res 20:319–336
Hall H, Sallemark M, Jerning E (1986) Effects of remoxipride and some related new substituted salicylamides on rat brain receptors. Acta Pharmacol Toxicol 58:61–70
Hall H, Farde L, Sedvall G (1988) Human dopamine receptor subtypes — in vitro binding analysis using 3H-SCH 23390 and 3H-raclopride. J Neural Transm 1988, 73:7–21
Hyttel J, Larsen J-J, Christensen AV, Arnt J (1985) Receptor-binding profiles of neuroleptics. In: Casey DE, Chase TN, Christensen AV, Gerlach J (eds) Psychopharmacology Suppl 2. Dyskinesia — research and treatment. Springer-Verlag, Berlin Heidelberg New York, pp 9–18
Meltzer HY, Goode DJ, Fang VS (1978) The effect of psychotropic drugs on endocrine function. In: Lipton MA, Di Mascio A, Killam KF (eds) Psychopharmacology. A generation of progress. Raven Press, New York, pp 509–529
Ögren SO, Hall H, Köhler C, Magnusson O, Lindbom LO, Angeby K, Florvall L (1984) Remoxipride, a new potential antipsychotic compound with selective antidopamiergic actions in the rat brain. Eur J Pharmacol 102:459–474
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grind, M., Nilsson, MI., Nilsson, L. et al. Remoxipride — a new potential antipsychotic compound. Psychopharmacology 98, 304–309 (1989). https://doi.org/10.1007/BF00451679
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00451679