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Titolo:
TRIADIMEFON AND TRIADIMENOL - EFFECTS ON MONOAMINE UPTAKE AND RELEASE
Autore:
WALKER QD; MAILMAN RB;
Indirizzi:
UNIV N CAROLINA,SCH MED,CURRICULUM TOXICOL CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,CURRICULUM TOXICOL CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,DEPT PSYCHIAT CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,DEPT MED CHEM CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,DEPT PHARMACOL CHAPEL HILL NC 27599 UNIV N CAROLINA,SCH MED,UNC NEUROSCI CTR CHAPEL HILL NC 27599
Titolo Testata:
Toxicology and applied pharmacology
fascicolo: 2, volume: 139, anno: 1996,
pagine: 227 - 233
SICI:
0041-008X(1996)139:2<227:TAT-EO>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINE UPTAKE; RAT STRIATUM; TRIAZOLE FUNGICIDE; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; STEREOTYPED BEHAVIOR; PREFRONTAL CORTEX; NEURONAL DOPAMINE; MOTOR-ACTIVITY; D-AMPHETAMINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
Q.D. Walker e R.B. Mailman, "TRIADIMEFON AND TRIADIMENOL - EFFECTS ON MONOAMINE UPTAKE AND RELEASE", Toxicology and applied pharmacology, 139(2), 1996, pp. 227-233

Abstract

Acute administration of the agricultural fungicide triadimefon produced a neurotoxic syndrome in rats characterized by increased motor activity, stereotyped behaviors, and altered monoamine metabolism, Triadimenol, a metabolite of triadimefon in mammals, plants, and soil, also increased motor activity in rodents, To test the hypothesis that triadimefon and triadimenol are indirect-acting dopamine agonists, the present studies examined their abilities to inhibit monoamine uptake, bind to the dopamine transporter, and stimulate dopamine efflux in rat brain tissue, in vitro. Both triazoles inhibited the uptake of dopamine instriatal synaptosomal preparations. Triadimefon was 100-fold less potent than GBR12909, a prototypical inhibitor of dopamine uptake (IC50 =4.7 mu M vs, 37.2 nM, respectively), and triadimenol was about three-fold less potent than triadimefon, Triadimefon also weakly inhibited the uptake of norepinephrine in cortical synaptosomes IC50 = 22.4 mu M), but neither compound blocked the uptake of serotonin in cortical synaptosomes (IC50s > 100 mu M). Triadimefon and triadimenol had similar affinity for [H-3]mazindol binding sites on the dopamine transporter (IC50s approximate to 1-1.5 mu M, only two- to three-fold greater than GBR12909). Neither triadimefon nor triadimenol (0.01-100 mu M) increased basal efflux of [H-3]DA that had been preloaded into striatal minces in vitro. An unexpected result was that GBR12909 (10 mu M) increasedbasal efflux of [H-3]DA by 71%, suggesting that this compound has DA releasing properties. These data suggest that increased synaptic concentrations of dopamine due to inhibition of dopamine uptake may play animportant role in the neurobehavioral effects of triadimefon and triadimenol. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 10:53:16