Titre du document / Document title

Comparative central nervous system effects and pharmacokinetics of neu-metoclopramide and metoclopramide in healthy volunteers

Auteur(s) / Author(s)

ROTMENSCH H. H. ⁽¹⁾ ; MOULD G. P. ⁽²⁾ ; SUTTON J. A. ⁽²⁾ ; KILMINSTER S. ⁽²⁾ ; MOLLER C. ⁽³⁾ ; PERO R. W. ^{(3 4)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Cato Research Israel and Souraski Medical Center, Tel-Aviv, ISRAEL
⁽²⁾ Guildford Clinical Pharmacology Unit, The Surrey County Hospital, Guildford, Surrey, ROYAUME-UNI
⁽³⁾ Oxigene Inc., Lund, SUEDE
⁽⁴⁾ Department of Molecular Ecogenetics, Lund University, Lund, SUEDE

Résumé / Abstract

Metoclopramide, a drug used for the relief of nausea and emesis, is currently under development as a radio- and chemosensitizing agent. Its usefulness in high doses, however, is limited by its central nervous system side effects. Neu-metoclopramide (NeuSensamide), a novel, concentrated, phosphate-buffered, pH-adjusted (pH = 6.5-7.0) formulation of metoclopramide, has been shown to have an improved side-effect profile in animal studies. The present double-blind, four-way crossover study compared the central nervous system effects and pharmacokinetics of neu-metoclopramide (intravenously and intramuscularly at 1.8 mg/kg) with intravenous metoclopramide and intramuscular placebo in 19 healthy male volunteers. Eight participants withdrew from the study, one because of noncompliance and seven because of adverse events. A total of 28 central nervous system events were observed with intravenous metoclopramide administration, whereas 16, 15, and 6 such events were attributed to intravenous neu-metoclopramide, intramuscular neu-metoclopramide, and placebo, respectively. Extrapyramidal effects occurred on 10 occasions: 7 after intravenous metoclopramide, 2 after intravenous neu-metoclopramide, and 1 after intramuscular neu-metoclopramide. No significant differences were observed in the pharmacokinetic profiles of the three formulations of metoclopramide. It may be speculated, therefore, that the molecular conformational changes inherent to neu-metoclopramide result in a reduced side-effect profile compared with conventional metoclopramide formulations.

Revue / Journal Title

Journal of clinical pharmacology   ISSN 0091-2700   CODEN JCPCBR 

Source / Source

1997, vol. 37, n^o3, pp. 222-228 (20 ref.)

Langue / Language

Anglais

Editeur / Publisher

Sage Science, Thousand Oaks, CA, ETATS-UNIS  (1973) (Revue)

Mots-clés anglais / English Keywords

Metoclopramide ; Structure activity relation ; Comparative study ; Antiemetic ; Extrapyramidal syndrome ; Dopamine antagonist ; Pharmacokinetics ; Human ; Biological activity ; Central nervous system ; Double blind study ; Crossover study ; Placebo ; Intravenous administration ; Intramuscular administration ; Toxicity ; Secondary effect ; Benzamide derivatives ; D2 Dopamine receptor ; Nervous system diseases ; Central nervous system disease ; Cerebral disorder ;

Mots-clés français / French Keywords

Métoclopramide ; Relation structure activité ; Etude comparative ; Antiémétique ; Extrapyramidal syndrome ; Antagoniste dopamine ; Pharmacocinétique ; Homme ; Activité biologique ; Système nerveux central ; Etude double insu ; Essai croisé ; Placebo ; Voie intraveineuse ; Voie intramusculaire ; Toxicité ; Effet secondaire ; Benzamide dérivé ; Récepteur dopaminergique D2 ; Neu-Métoclopramide ; Système nerveux pathologie ; Système nerveux central pathologie ; Encéphale pathologie ;

Mots-clés espagnols / Spanish Keywords

Metoclopramida ; Relación estructura actividad ; Estudio comparativo ; Antiemético ; Extrapiramidal síndrome ; Antagonista dopamina ; Farmacocinética ; Hombre ; Actividad biológica ; Sistema nervioso central ; Estudio doble ciego ; Ensayo cruzado ; Placebo ; Vía intravenosa ; Vía intramuscular ; Toxicidad ; Efecto secundario ; Benzamida derivado ; Receptor dopaminérgico D2 ; Sistema nervioso patología ; Sistema nervosio central patología ; Encéfalo patología ;

Localisation / Location

INIST-CNRS, Cote INIST : 10257, 35400006491428.0070