Studies of the pharmacology of a new antidepressant, S1694.
A new antidepressive drug, S1694, produces increased locomotor activity (LA) in mice, but less so than d-amphetamine. This effect is decreased by pimozide, phenoxybenzamine, as well as by pretreatment of the animals with reserpine or alpha-methyl-p-tyrosine methyl ester (H44/68). S1694 inhibits active dopamine (DA) uptake into rat striatal synaptosomes, but not noradrenaline (NA) uptake into rat hypothalamic synaptosomes, or serotonin (5-HT) uptake into rat midbrain synaptosomes, in the concentrations used. The inhibition of DA uptake appears tp be competitive and the inhibition constant estimated is 1,3 X 10(-6) M. In addition, S1694 releases DA in the same concentrations, and NA as well as 5HT at higher concentrations. It is concluded that S1694 activates LA primarily by inhibitionof DA re-uptake and DA release. The central DA system activation may be important in the antidepressive effect.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D003986:Dibenzocycloheptenes; D018377:Neurotransmitter Agents; D004298:Dopamine