title: Pharmacological profile of the abeorphine 201-678, a potent orally active and long lasting dopamine agonist.
abstract: The central dopaminergic effects of an abeorphine derivative 201-678 were compared to those of apomorphine and bromocriptine in different model systems. After oral administration, this compound induced contralateral turning in rats with 6-hydroxydopamine induced nigral lesions and exhibited strong anti-akinetic properties in rats with 6-hydroxydopamine induced hypothalamic lesions. It decreased dopamine metabolism in striatum and cortex, but did not modify noradrenaline and serotonin metabolism in the rat brain. 201-678 counteracted the in vivo increase of tyrosine hydroxylase activity induced by gamma-butyrolactone. In vitro it stimulated DA-sensitive adenylate cyclase and inhibited acetylcholine release from rat striatal slices. This compound had high affinity for 3H-dopamine and 3H-clonidine binding sites. These results indicate that 201-678 is a potent, orally active dopamine agonist with a long duration of action. Furthermore it appears more selective than other dopaminergic drugs.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003000:Clonidine / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000032:analysis; D007031:Hypothalamus / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000032:analysis; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology
chemical_list: D007211:Indoles; D011954:Receptors, Dopamine; D012701:Serotonin; D007980:Levodopa; C047807:CI 201-678; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003000:Clonidine; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine