PT  - JOURNAL ARTICLE
AU  - C D Kurth
AU  - C Monitto
AU  - M L Albuquerque
AU  - P Feuer
AU  - E Anday
AU  - L Shaw
TI  - Cocaine and its metabolites constrict cerebral arterioles in newborn pigs.
DP  - 1993 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 587--591
VI  - 265
IP  - 2
4099  - http://jpet.aspetjournals.org/content/265/2/587.short
4100  - http://jpet.aspetjournals.org/content/265/2/587.full
SO  - J Pharmacol Exp Ther1993 May 01; 265
AB  - We examined the effect of cocaine and several of its metabolites on cerebral arterioles in newborn pigs and evaluated the sympathomimetic properties of each of the compounds as a vasoactive mechanism. After piglets were equipped with closed cranial windows, compounds were suffused over the brain surface and pial arteriolar diameter (base line, approximately 100 microns) was recorded. Cocaine, cocaethylene, norcocaine, ecogonine, benzoylecgonine and ecgonine methylester each caused a dose-dependent (10(-8) M to 10(-4) M) decrease in pial arteriolar diameter: maximum percent reductions in diameter induced by each compound (10(-4) M) were, respectively, 12 +/- 1, 12 +/- 2, 11 +/- 1, 7 +/- 1, 7 +/- 2 and 5 +/- 1. In analyzing the dose-response curves, cocaethylene was the most potent vasoconstrictor, followed by cocaine, norcocaine and then ecogonine, benzoylecgonine and ecgonine methylester. Cerebral vasoconstriction induced by topically applied norepinephrine was enhanced by cocaine, norcocaine and cocaethylene, but not by the other three metabolites. Topical application of phentolamine failed to block vasoconstriction elicited by cocaine or its metabolites, although it did block vasoconstriction elicited by norepinephrine. These observations indicate that cocaine and its metabolites constrict the immature cerebrovasculature by a non-sympathomimetic mechanism.