Benzodiazepine receptor ligands. 7. Synthesis and pharmacological evaluation of new 3-esters of the 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide. 3-(2-Thienylmethoxycarbonyl) derivative: an anxioselective agent in rodents.
The synthesis and binding study of new 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 3-ester compounds are reported. A pharmacological evaluation of the high-affinity ligands 1-4 belonging to the 3-heteroarylester series is made. The 3-(2-thienylmethoxycarbonyl) derivative 4 stands out from the other heteroarylesters and is found, using nine different behavioral methods, to be a functionally selective ligand in vivo: it shows anxiolytic-like activity in the conflict models (light-dark box and plus maze test) similarly to diazepam, without any sedative and amnesic properties or interference from alcohol.
Costanzo
Annarella
A
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Firenze, Via Gino Capponi 9, 50121 Firenze Italy. annarella.costanzo@unifi.it
Guerrini
Gabriella
G
Ciciani
Giovanna
G
Bruni
Fabrizio
F
Costagli
Camilla
C
Selleri
Silvia
S
Besnard
François
F
Costa
Barbara
B
Martini
Claudia
C
Malmberg-Aiello
Petra
P
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D018682:GABA Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008568:Memory / Q000187:drug effects; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D009465:Neuromuscular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship; D014227:Triazines
C470203:3-(2-thienylmethoxycarbonyl)-8-chloropyrazolo(5,1-c)(1,2,4)benzotriazine 5-oxide; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D003497:Cyclic N-Oxides; D018682:GABA Agents; D006575:Heterocyclic Compounds, 3-Ring; D008024:Ligands; D009465:Neuromuscular Agents; D011963:Receptors, GABA-A; D014227:Triazines; D000431:Ethanol