6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A new class of benzodiazepine receptor ligands.
Some 6-(alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (pentylenetetrazole test, mice) and anticonflict activity (Vogel test, rat) in vivo. Separation between the doses causing anticonflict effects (Vogel test, rat) and those impairing motor coordination (rotarod test, rat) has been shown for N,N-bis(2-methoxyethyl)-3-(4-methoxyphenyl)-1,2,4-triazolo[3,4-a] phthalazin-6-amine (80). This compound, unlike diazepam, was inactive in counteracting the strychnine (mouse) and maximal electroshock (mouse) induced convulsions and in the "aggressive monkey" model. These differences from the classical benzodiazepines in the animal tests indicate that 80 may have some selective anxiolytic activity.
Tarzia
G
G
Department of Chemistry, Lepetit Research Laboratories, Milan, Italy.
Occelli
E
E
Toja
E
E
Barone
D
D
Corsico
N
N
Gallico
L
L
Luzzani
F
F
D000374:Aggression / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology*; D003220:Conflict, Psychological; D066298:In Vitro Techniques; D008024:Ligands; D008251:Macaca; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D008024:Ligands; D011963:Receptors, GABA-A