title: Benzodiazepine receptor ligands. Synthesis and preliminary pharmacological evaluation of some 3-aryl-6-thioalkyl-, 3-aryl-6-alkylsulphinyl-, 3-aryl-6-alkylsulphonyl-, and 3-aryl-6-alkoxy-1,2,4-triazolo[3,4-a]phthalazines.
abstract: A series of 3-aryl-6-alkoxy- and some 3-aryl-6-thioalkyl-, 3-aryl-6-alkylsulphinyl-, and 3-aryl-6-alkylsulphonyl-1,2,4-triazolo[3,4-a]phthalazines were synthesised and tested for inhibition of the in vitro binding of 3H-Diazepam to benzodiazepine receptors in membranes isolated from rat brain synaptosomes. 6-Alkoxy-3-(4'-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazines were more active than or as active as diazepam in the binding assay (Ki nM) but unlike diazepam their binding to the benzodiazepine receptors was not enhanced by 4-aminobutyric acid. These compounds did not antagonize pentylenetetrazole induced convulsions and were inactive in modifying the conditioned behaviour of rats. Compound (II a) counteracted the muscle relaxant effects of diazepam (traction test). These results suggest that (II a) may be a benzodiazepine receptor antagonist.
authors.affiliation: Merrell-Dow Research Institute, Lepetit Research Centre, Gerenzano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tarzia
authors.forename: E
authors.initials: E
authors.lastname: Occelli
authors.forename: N
authors.initials: N
authors.lastname: Corsico
authors.forename: F
authors.initials: F
authors.lastname: Luzzani
authors.forename: D
authors.initials: D
authors.lastname: Barone
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D001362:Avoidance Learning / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis; D010793:Phthalazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011724:Pyridazines / Q000138:chemical synthesis*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013440:Sulfides / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D009125:Muscle Relaxants, Central; D010793:Phthalazines; D011724:Pyridazines; D011963:Receptors, GABA-A; D013440:Sulfides; D013450:Sulfones; D014230:Triazoles; D005680:gamma-Aminobutyric Acid