Ecgonine methyl ester, a major cocaine metabolite, causes cerebral vasodilation in neonatal sheep

Pediatric Research
M A PaneC A Gleason

Abstract

Maternal cocaine abuse has been associated with fetal and neonatal neurologic abnormalities, including hemorrhagic cerebral infarctions, but the mechanisms for cocaine's cerebral effects are unknown. We previously showed that acute cocaine injection causes cerebral vasodilation in cats and immature sheep; others have shown that cocaine causes cerebral vasoconstriction in piglets and in pressurized neonatal sheep arteries. Although methodologic and species differences may explain these conflicting results, we tested another possibility; that is, that ecgonine methyl ester (EME), a major cocaine metabolite in sheep, causes cerebral vasodilation and may account, in part, for cocaine's vascular effects. We studied the cerebral effects of a single i.v. injection of EME (2.5 mg/kg) in eight chronically catheterized, unanesthetized neonatal sheep (4 +/- 2 d old). We measured cerebral hemisphere blood flow (CBF) using radiolabeled microspheres, mean arterial pressure, heart rate, and arteriovenous oxygen content, and we calculated cerebral oxygen consumption (CMRo2) and cerebrovascular resistance at baseline and 0.5, 2, 5, and 60 min after EME injection. EME injection had no systemic effects, including no changes in mean arterial press...Continue Reading

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Citations

Nov 22, 2001·European Journal of Pharmacology·C W SchindlerS R Goldberg
May 13, 1999·Critical Care Medicine·T P O'BrienC A Gleason
Aug 24, 2002·Archives of Disease in Childhood. Fetal and Neonatal Edition·H S BadaP L Maza
Feb 9, 2020·Psychopharmacology·Stephen H Curry, Matthew Marler
Jul 19, 2000·American Journal of Physiology. Heart and Circulatory Physiology·R RobinsonC A Gleason
Oct 6, 2004·Journal of Toxicology. Clinical Toxicology·Robert S HoffmanLewis R Goldfrank
Sep 1, 2004·Experimental Biology and Medicine·Massroor PourcyrousCharles W Leffler

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