Structure-activity relationships of some novel coronary dilator derivatives of palmitoyl carnitine in the rat isolated heart.
The structure-activity relationships of some novel coronary dilator derivatives of palmitoyl carnitine in the rat isolated perfused heart are described. It has been shown previously that esterification of palmitoyl carnitine changes the activity of the compound from a coronary constrictor to a coronary dilator. In this study, it was found that the ester group is not a necessary requirement for coronary dilator activity, but only the absence of the negatively charged carboxylic acid group of palmitoyl carnitine, as compounds containing an ethyl group in place of the ester group were also active coronary dilators. Furthermore, substituting the methyl groups attached to the nitrogen atom of the molecule profoundly altered coronary dilator activity. A quaternary ammonium group was a necessary requirement for potent coronary dilator activity.
Reeves
K A
KA
School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Avon, UK.
Dewar
G H
GH
Rad-Niknam
M
M
Woodward
B
B
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010172:Palmitoylcarnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D010172:Palmitoylcarnitine