[The acute and subchronic effects of hemantane on [3H]-dopamine reuptake in rat striatal synaptosomes ex vivo].
The ex vivo effects of the new antiparkinsonian drug (adamantane derivative) hemantane on the [3H]-dopamine reuptake rate (V) in striatum have been studied upon acute and subchronic administration of the drug in Wistar rats. The [3H]-dopamine reuptake was measured in striatal synaptosomes isolated from rats decapitated 1 hour after drug injection (40 mg/kg, i.p.), and in synaptosomes of rats treated for 7 days with hemantane (single daily dose, 20 mg/kg, i.p.). The acute experiment resulted in a significant (30%) decrease in the apparent Vmax of [3H]-dopamine reuptake, while the value of the apparent Km remained unchanged. The data obtained indicate that hemantane suppresses the DA transporter function within physiological concentration range via noncompetitive mode. In contrast, subchronic drug administration increases by 17% the apparent Vmax. These results demonstrate the active participation of presynaptic transport mechanism in dopamine-positive effects of hemantane.
Abaimov
D A
DA
Kovalev
G I
GI
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000978:Antiparkinson Agents; D018765:Dopamine Uptake Inhibitors; C526127:hemantane; D000218:Adamantane; D004298:Dopamine