Progesterone antagonist mifepristone (RU 486) decreases cardiotoxicity of cocaine.
RU 486, a potent progesterone antagonist, was used to determine whether RU 486 blocks the enhanced cardiotoxicity of cocaine mediated by progesterone upon rat papillary muscles. Groups of nonpregnant rats were pretreated with: progesterone for 3 days (n = 12); progesterone + RU 486 for 3 days (n = 12); progesterone for 3 days + single low dose RU 486, progesterone for 3 days + single high dose RU 486, and RU 486 for 3 days (n = 6); or were untreated (n = 12). Papillary muscles from these groups were electrically paced during exposure to cocaine concentrations ranging from 10(-14) M to 10(-3) M. One group (n = 6) was pretreated with RU 486, but not exposed to cocaine. The results showed that all muscles from rats pretreated with RU 486 for 3 days were functional when exposed to cocaine concentrations one to four orders of magnitude higher than tolerated by muscles from untreated or progesterone-treated rats. As indicated by alterations in contraction response patterns, RU 486 treatment for 3 days reversed progesterone-enhanced cardiotoxicity of cocaine. Single low dose and high dose RU 486 administrations also reversed progesterone's effects upon cocaine-induced cardiotoxicity.
Sharma
A
A
Department of Obstetrics and Gynecology, University of Rochester Medical Center, New York 14620.
Plessinger
M A
MA
Miller
R K
RK
Woods
J R
JR
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D015735:Mifepristone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000037:antagonists & inhibitors*; D051381:Rats
D004338:Drug Combinations; D015735:Mifepristone; D011374:Progesterone; D003042:Cocaine