Effects of dopamine partial-agonist aminoergolines on dopamine metabolism in limbic and extrapyramidal regions of rat brain.

Abstract

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.

• Authors: R J Baldessarini, E R Marsh, D Huston-Lyons
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 47 Issue 10 Pg. 1917-9 (May 18 1994) ISSN: 0006-2952 [Print] England
• PMID: 7911303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dopamine Agents
• Ergolines
• Hydrazines
• N-(2,6-dimethylergoline-8-yl)-2,2-dimethylpropanamide
• N-(2-chloro-6-methylergoline-8-yl)-2,2-dimethylpropanamide
• Dihydroxyphenylalanine
• 3-hydroxybenzylhydrazine
• 4-Butyrolactone
• Dopamine

Topics

• 4-Butyrolactone (pharmacology)
• Animals
• Dihydroxyphenylalanine (analysis)
• Dopamine (metabolism)
• Dopamine Agents (pharmacology)
• Dose-Response Relationship, Drug
• Ergolines (pharmacology)
• Extrapyramidal Tracts (drug effects, metabolism)
• Hydrazines (pharmacology)
• Limbic System (drug effects, metabolism)
• Male
• Rats
• Rats, Sprague-Dawley