Comparison of the in vivo pharmacological profiles of sabeluzole and its enantiomers

Abstract

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.

Chronic treatment with sabeluzole protects cultured rat brain neurons from the neurotoxic effects of excitatory amino acids

“…A 0 1992 WILEY-LISS, INC. similar improvement of memory was obtained in a pilot study with patients suffering from age-associated memory impairment (Clincke et al, 1992;Tritsmans et al, 1990). Apart from cognitive enhancing activity, sabeluzole has also pronounced antihypoxic and anticonvulsant properties (Wauquier et al, 1986;Werbrouck et al, 1991).…”

Non-Imidazole Histamine H3 Ligands, Part 2: New 2-Substituted Benzothiazoles as Histamine H3 Antagonists

“…Non-imidazole structures such as betahistine [17] , phencyclidine [18] , dimaprit [19,20] , clozapine [21] , and sabeluzole [22] which is a benzothiazole derivative, have only weak H 3 antagonist activity. Very recently, Ganellin et al [23] reported a novel series of homologues O and S isosteric tertiary amines of N-ethyl-N-(4-phenylbutyl)amine as potent non-imidazole histamine H 3 receptor antagonists.…”

Facile, alternative route to Lubeluzole, its enantiomer, and the racemate

“…The next step was the conversion of the carbamate 2 into the corresponding 2-benzothiazolyl derivative 3. An earlier two-step procedure 12,21,22 was reported to afford 3 by reaction of 2 with isothiocyanatobenzene to give a thiourea intermediate, which in turn underwent oxidative cyclization affording the desired product (overall yield about 71%). Taking inspiration from a procedure reported in the literature for the preparation of various 2-methylamino-and 2-dimethylamino benzocondensed azoles, 23 we explored the possibility of performing the direct coupling of commercially available 2-chlorobenzothiazole with 2.…”