Pharmacological studies on a new thymoleptic antidepressant, 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32).
Some pharmacological actions of 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS-32), a newly synthesized indazole derivative, were investigated in comparison with imipramine. FS-32 showed anti-reserpine activity in a dose-dependent manner, whereas imipramine exhibited a bell-shaped dose-response pattern. Catecholaminergic potentiation was demonstrated with FS-32. The results obtained from a norepinephrine potentiation test in vitro suggest that FS-32 may act in a manner qualitatively different from the tricyclic antidepressant. FS-32 produced a definite suppressive effect on isolation-induced fighting without affecting coordinated motor activity and on the duration of afterdischarge elicited by electrical stimulation to the amygdala or the hippocampus without producing a slow wave pattern in the EEG. Similar effects on fighting behavior and the afterdischarge were shown under imipramine with a slight motor incoordination and with a slow wave pattern, respectively. FS-32 produced practically no peripheral anti-cholinergic action, while it antagonized central cholinergic activity. FS-32 tended to produce an increase in chatecholamine content in the brain without MAO or COMT inhibitory activity. Norepinephrine uptake was inhibited by FS-32, but less than by imipramine. These pharmacological properties suggest a potential clinical utility of FS-32 as an antidepressant possessing thymoleptic activities.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology; D002415:Cats; D004285:Dogs; D004569:Electroencephalography; D005260:Female; D006168:Guinea Pigs; D000882:Haplorhini; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010830:Physostigmine / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors; D014203:Tremorine / Q000037:antagonists & inhibitors
D000928:Antidepressive Agents; D001463:Barbiturates; D001679:Biogenic Amines; D002395:Catecholamines; D007191:Indazoles; D011720:Pyrazoles; D007980:Levodopa; C020952:1-(3-(dimethylamino)propyl)-5-methyl-3- phenyl-1H-indazole; D012110:Reserpine; D010830:Physostigmine; D000661:Amphetamine; D000109:Acetylcholine; D014203:Tremorine