Molecular requirement for anticonvulsant activity in a series of thiazolo-1,4-benzodiazepine derivatives and comparison with classical benzodiazepines

General Pharmacology
G B DeSarroA DeSarro

Abstract

1. The behavioural and anticonvulsant effects of several thiazolo[3,2-d][1,4]benzodiazepines (TBZ) were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. Anticonvulsant effects on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) were evaluated in DBA/2 mice placed singly under a perspex dome. 3. Hypothermic activity was observed after the highest doses of the benzodiazepines studied. 4. In addition, some TBZ were examined for anticonvulsant properties with respect to clonus induced by pentylenetetrazol. 5. Our study demonstrated that some thiazolobenzodiazepine derivatives were more potent than clobazam, desmethylclobazam and chlordiazepoxide, and less potent than diazepam, desmethyldiazepam and alprazolam. 6. In the series of tricyclic benzodiazepines, thiazole nucleus fusion to the "d" edge of the 7-membered ring results in an effective increase of the energy barrier for the heptatomic system reversal, and is probably responsible for, jointly with the lack of C=N double bonds, lower activity with respect to the 1,4-benzodiazepine precursors. 7. The potency of various thiazolobenzodiazepine derivatives as inhibitors of specific [3H]flu...Continue Reading

References

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Citations

Sep 1, 1996·General Pharmacology·G De SarroA De Sarro
Sep 1, 1997·Pharmacology, Biochemistry, and Behavior·G De SarroA De Sarro
Dec 1, 1993·Bioorganic & Medicinal Chemistry·F CampagnaG B De Sarro
Jul 14, 2001·Indian Journal of Pediatrics·V JainS Singhi
Jun 15, 2012·Archiv der Pharmazie·Awatef A FaragSamir Y Abbas

Related Concepts

Acoustic Stimulation
Metazoa
Anticonvulsants
Benzodiazepines
Romazicon
Flunitrazepam-ratiopharm
Injections, Intraperitoneal
Mice, Inbred DBA
Pentazol
Non-epileptic Convulsion

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