title: Effect of lergotrile on 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain.
abstract: Lergotrile, a dopamine agonist, lowered whole brain DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rats. At low doses down to 0.5 mg/kg of lergotrile mesylate, this effect occurred within 30 min, whereas at higher doses (20 mg/kg) the decline in DOPAC was delayed. The decrease in DOPAC persisted for several hours and presumably resulted from a compensatory decrease in brain dopamine turnover secondary to receptor stimulation by lergotrile. Other indications of decreased brain dopamine turnover after lergotrile included (a) a slower decline in dopamine concentration after synthesis inhibition by alpha-methyltyrosine, (b) a slower decline in alpha-methyl-m-tyramine, a false transmitter that is stored and released by dopamine neurons, and (c) a decreased accumulation of dopamine in response to gamma-butyrolactone, an agent that blocks firing and dopamine release by dopamine neurons. Lergotrile mesylate (20 mg/kg) also increased brain levels of 5-hydroxyindoleacetic acid and of 3-methoxy-4-hydroxyphenylethylene glycol sulfate, metabolites of serotonin and norepinephrine, respectively, and these increases were not antagonized by spiperone, a dopamine receptor antagonist.
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D015107:4-Butyrolactone / Q000494:pharmacology; D000097:Acetonitriles / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D010136:p-Hydroxyamphetamine / Q000378:metabolism
chemical_list: D000097:Acetonitriles; D004873:Ergolines; D010648:Phenylacetates; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D010136:p-Hydroxyamphetamine; D015107:4-Butyrolactone; D004298:Dopamine; D009638:Norepinephrine