Inhibition of (3H)-dopamine uptake into rat brain synaptosomes by the new non-tricyclic antidepressants, FS32 and FS97.
The effects of new non-tricyclic antidepressants, FS32 and its desmethylated compound (FS97), on the uptake of (3H)-dopamine (DA) by rat purified whole brain synaptosomes and the striatal synaptosomes were studied. The uptake into synaptosomes was time- and temperature-dependent and was saturable with a Km value of 9.1 X 10(-8) M. The inhibiting activities of both compounds were comparable to those of amitriptyline, nortriptyline and iprindole, and were nearly twice the activity of imipramine and desipramine. The kinetic constants indicated that both FS32 and FS97 were competitive inhibitors of (3H)-DA uptake. Neither drug caused a significant release of (3H)-DA from the synaptosomes.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000928:Antidepressive Agents; D007191:Indazoles; D009419:Nerve Tissue Proteins; D011720:Pyrazoles; C020952:1-(3-(dimethylamino)propyl)-5-methyl-3- phenyl-1H-indazole; C025243:1-(3-(methylamino)-propyl)-5-methyl-3-phenyl-1H-indazole; D004298:Dopamine