TY - JOUR T1 - Interactions between Cocaine and Dopamine Agonists on Cardiovascular Function in Squirrel Monkeys JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 180 LP - 187 DO - 10.1124/jpet.300.1.180 VL - 300 IS - 1 AU - C. W. Schindler AU - J. P. Gilman AU - J. Bergman AU - N. K. Mello AU - R. L. Woosley AU - S. R. Goldberg Y1 - 2002/01/01 UR - http://jpet.aspetjournals.org/content/300/1/180.abstract N2 - Conscious squirrel monkeys were treated i.v. with cocaine and various dopamine agonist drugs. Cocaine produced a dose-dependent increase in blood pressure, heart rate, and the rate-pressure product (RPP). The dopamine D1 receptor agonist (±)-6-chloro-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 82958) produced effects comparable to cocaine. The D1 agonist (±)-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) also produced increases in blood pressure and heart rate but was much less potent than either cocaine or SKF 82958. The partial D1 agonist (±)-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SKF 77434) did not significantly affect any cardiovascular parameters. The D2 agonist quinpirole slightly decreased blood pressure and increased heart rate. As such, the RPP only slightly increased. The selective dopamine uptake inhibitor 1-[2-[bis-(4-fluorphenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909) produced increases in blood pressure, heart rate, and RPP, but again these effects were smaller and only seen at doses higher than cocaine. Effects similar to those with GBR 12909 were seen with the dopamine autoreceptor antagonistcis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232). The combination of GBR 12909, SKF 82958, or SKF 77434 with cocaine produced effects that were clearly subadditive. The effects of quinpirole in combination with cocaine were comparable to, or lower than, those of cocaine alone on blood pressure and RPP. The effects on heart rate were additive. Only UH 232 produced additive effects with cocaine for all three measures. As dopamine agonists have been proposed as potential treatments for cocaine abuse, these results suggest that dopamine D1 agonists and uptake inhibitors can be used safely in combination with cocaine. Caution may be warranted, however, with the use of dopamine autoreceptor antagonists in the treatment of cocaine abuse. RPPrate-pressure productAUCarea under the curveSKF 82958(±)-6-chloro-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromideSKF 81297(±)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromideSKF 77434 (±)-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochlorideGBR 12909, 1-[2-[bis-(4-fluorphenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazineUH 232 cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralinSCH 23390(+)-7-chloro-9-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride ER -