Elsevier

Biochemical Pharmacology

Volume 33, Issue 19, 1 October 1984, Pages 2957-2960
Biochemical Pharmacology

Depletion of cardiac norepinephrine in rats and mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

https://doi.org/10.1016/0006-2952(84)90593-8Get rights and content

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a commercially available chemical reagent. Although little has been known about its biological effects, recently MPTP has been reported to cause irreversible Parkinson's disease-like symptoms in human and in monkeys. We describe here another pharmacologic effect of MPTP, the ability to deplete cardiac norepinephrine in rats and mice. In mice, cardiac norepinephrine concentration decreased within 1 hr, was maximally depleted at 24 hr, and recovered by 4–7 days after i.p. injection of a 32 mg/kg dose of MPTP. The depletion was antagonized by desipramine pretreatment, as was norepinephrine depletion by tyramine. In rats, cardiac norepinephrine depletion by 10–30 mg/kg, i.p., doses of MPTP was accompanied by depletion of cardiac dopamine and norepinephrine in the mesentric artery. In rats and in mice, norepinephrine in brain was affected to a smaller degree than was norepinephrine in heart, and dopamine in brain was depleted very little if at all. In spontaneously hypertensive rats, the depletion of cardiac norepinephrine was associated with a marked antihypertensive effect. The p-hydroxy analog of MPTP did not deplete cardiac norepinephrine in rats, indicating that its possible fermation as a metabolite of MPTP was not involved in the depletion of cardiac norepinephrine. These findings extend the spectrum of known pharmacologic effects of MPTP.

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