Neuropharmacological screening of two 1,5-benzodiazepine compounds in mice

• Published in: Comptes rendus. Biologies Vol. 333; no. 3; p. 214
• Main Authors: Ben-Cherif, Wafa, Gharbi, Rafik, Sebai, Hichem, Dridi, Dorra, Boughattas, Naceur A, Ben-Attia, Mossadok
• Format: Journal Article
• Language: English
• Published: France 01-03-2010
• Subjects: Animals; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Benzodiazepines - therapeutic use; Benzodiazepinones - therapeutic use; Benzopyrans - therapeutic use; Diazepam - pharmacology; Diazepam - therapeutic use; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Epilepsy, Tonic-Clonic - drug therapy; Epilepsy, Tonic-Clonic - prevention & control; Flunitrazepam - pharmacology; Flunitrazepam - therapeutic use; GABA Agonists - chemistry; GABA Agonists - pharmacology; GABA Agonists - therapeutic use; Hexobarbital - pharmacology; Hypnotics and Sedatives - chemistry; Hypnotics and Sedatives - pharmacology; Hypnotics and Sedatives - therapeutic use; Male; Mice; Molecular Structure; Random Allocation; Receptors, GABA-A - drug effects; Receptors, GABA-A - physiology; Sleep - drug effects
• ISSN: 1768-3238
• DOI: 10.1016/j.crvi.2009.09.015

This work investigates whether the two 1,5-benzodiazepine compounds: 4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-one (RG0501) and Benzopyrano [4,3-c] 1,5-benzodiazepine (RG0502) have any neuropharmacological activities. Diazepam and Flunitrazepam were used as drug references. The investigational 1,5-BDZ were tested in vivo for potentiating hexobarbital-induced sleep and pentylenetetrazole (PTZ)-induced seizures. Our study demonstrated that the increase of sleep duration was significantly higher with RG0501 as compared to RG0502. However, RG0502 anticonvulsant effect was more pronounced than that of RG0501 in the range dose of 6.25-37.5 mg.kg(-1). From the 50 mg.kg(-1) dose, RG0502 offered a protection against clonic-tonic seizures as well as lethality (p< or =0.05). The results showed that the required doses to obtain a pharmacological activity were more than those of the references. This difference could be related to the lack of specific substituants responsible for the pharmacological activity in the tested compounds.