Effects of dopamine partial-agonist aminoergolines on dopamine metabolism in limbic and extrapyramidal regions of rat brain.
The aminoergolines SDZ-208-911, -208-912, and -212-327, weak partial D2 agonists with agonist/antagonist properties, are proposed as potential atypical antipsychotic agents with limited risk of extrapyramidal effects or hyperprolactinemia. The in vivo effects on dopamine (DA) metabolism in limbic (accumbens) and extrapyramidal (striatum) regions of rat brain were evaluated by measuring the accumulation of L-dihydroxyphenylalanine (DOPA) after inhibiting decarboxylation alone ("open-loop" model) or with added gamma-butyrolactone (GBL, autoreceptor model). All three aminoergolines markedly increased DOPA in both regions, dose-dependently, with only minor decreases when GBL was included, and so evidently lack appreciable agonist activity at D2-like autoreceptors and resemble typical neuroleptics in stimulating DA synthesis, without regional selectivity.
Baldessarini
R J
RJ
Consolidated Department of Psychiatry, Harvard Medical School, Boston, MA.
Marsh
E R
ER
Huston-Lyons
D
D
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D004295:Dihydroxyphenylalanine / Q000032:analysis; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D005116:Extrapyramidal Tracts / Q000187:drug effects* / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D004873:Ergolines; D006834:Hydrazines; C062737:N-(2,6-dimethylergoline-8-yl)-2,2-dimethylpropanamide; C059362:N-(2-chloro-6-methylergoline-8-yl)-2,2-dimethylpropanamide; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D015107:4-Butyrolactone; D004298:Dopamine