RESUMO
We report the synthesis, stereochemistry and preliminary pharmacological evaluation of DCN 203-922, a novel ergot alkaloid of the cyclol type, which contains in its peptide moiety the uncommon amino acid L-allo-isoleucine.
Assuntos
Alcaloides de Claviceps/síntese química , Animais , Comportamento Animal/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Fenômenos Químicos , Química , Físico-Química , Cristalização , Alcaloides de Claviceps/farmacologia , Rim/efeitos dos fármacos , Conformação Molecular , Ratos , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Receptores de Dopamina D2 , Sono REM/efeitos dos fármacos , Vigília/efeitos dos fármacosRESUMO
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.
