Inhibition of dopamine uptake by a new psychostimulant mesocarb (Sydnocarb).
The effect of a new psychostimulant, mesocarb was determined on the in vitro uptake of biogenic amines into synaptosomes prepared from whole rat brain and various cerebral regions. Amphetamine was also examined as reference compound. On the other hand, the effects of mesocarb and amphetamine were compared in vivo on the uptake of catecholamines (CA) using an indirect method based on the inhibiton of cerebral CA depletion caused by intraventricularly injected 6-hydroxydopamine (6-OHDA). Mesocarb was found to block the synaptosomal uptake of dopamine (DA) in the striatum and whole brain more effectively than amphetamine, but inhibited the noradrenaline (NA) uptake into hypothalamus much less than amphetamine. The effect of mesocarb on 5-hydroxytryptamine (5HT) uptake was not significant, similarly as that of amphetamine. On the other hand, mesocarb inhibited the decrease of brain DA levels but had no protecting effect against NA depletion caused by 6-OHDA, in vivo. Amphetamine dose-dependently inhibited NA depletion caused by 6-OHDA but did not inhibit DA depletion. These findings indicate that mesocarb is a specific inhibitor of in vitro synaptosomal CA uptake, with an activity for striatal and whole brain DA uptake blockade much higher than that of amphetamine. The results also show that mesocarb is a selective inhibitor of DA uptake in vivo, in contrast to amphetamine, which preferentially blocks the uptake of NA in the brain. This difference may presumably be responsible for the different psychostimulatory action of the two compounds.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013558:Sydnones / Q000494:pharmacology*
D018492:Dopamine Antagonists; D010069:Oxadiazoles; D011619:Psychotropic Drugs; D013558:Sydnones; D000661:Amphetamine; C009257:sidnocarb; D004298:Dopamine; D009638:Norepinephrine