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Comparison of the in vivo pharmacological profiles of sabeluzole and its enantiomers
Author(s) -
Werbrouck Leen,
Megens Anton A. H. P.,
Stokbroekx Raymond A.,
Niemegeers Carlos J. E.
Publication year - 1991
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430240104
Subject(s) - enantiomer , potency , anticonvulsant , pharmacology , chemistry , in vivo , biological activity , stereochemistry , in vitro , medicine , epilepsy , biology , biochemistry , microbiology and biotechnology , psychiatry
Sabeluzole, a compound with pronounced cognitive enhancing, antihypoxic, and anticonvulsant properties, is the racemic mixture of the enantiomers R 84 439 (R‐configuration) and R 84 440 (S‐configuration). Sabeluzole and its separate enantiomers were compared in tests evaluating cognitive enhancing, antihypoxic, anticonvulsant, and secondary activity. Only small differences in potency were observed over species (mice, guinea pigs, and rats), routes of administration (i.p., s.c., and p.o.), and time intervals (ranging from 0.5 to 16 hr). R 84 440 was generally slightly more potent (up to 2.6 times) but also slightly shorter acting than R 84 439 (5 vs. 7 hr after s.c. administration in rats). The present data confirm and further extend the pharmacological profile of sabeluzole and indicate that both enantiomers contribute to its biological activity. Selection of one of the enantiomers instead of racemic sabeluzole provides no practical advantage in terms of potency, onset and duration of action, oral absorption, or therapeutic index.