Effects of phenylalkylamine calcium entry blockers on postischemic energy metabolism in the isolated perfused rat brain: stereoselective action of emopamil.
The purpose of the present investigation was to compare the effects of some phenylalkylamine calcium entry blockers on postischemic energy metabolism in the isolated perfused rat brain. To differentiate between calcium entry blockade and nonspecific effects the optically active stereoisomers of emopamil were investigated. At a concentration of 10 mumol/l both gallopamil and emopamil enhanced the postischemic restoration of high-energy phosphate levels. The racemic mixture and the (-)-enantiomer of emopamil and noremopamil caused similar metabolic changes at 1 mumol/l. The (+)-enantiomer of emopamil proved to be ineffective at either 1 or 10 mumol/l. The effects on energy metabolism were accompanied by an increase in the postischemic perfusion rate. The results suggest that the drug efficacy necessary to accelerate the restitution of postischemic energy metabolism is in the order of noremopamil greater than emopamil greater than gallopamil. The effects of the phenylalkylamine calcium entry blockers on energy metabolism are discussed in relation to vasodilation due to calcium entry blockade.
Weber
J
J
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, BRD.
Bielenberg
G W
GW
Krieglstein
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D005711:Gallopamil; D014700:Verapamil; C052752:emopamil