Pharmacological characteristics of the stereoisomers of carvedilol.
The racemic compound carvedilol possesses two complementary pharmacological effects, vasodilation and beta-blockade. The R- and S-enantiomers of carvedilol and the racemate were investigated with respect to the beta-blocking, vasodilating, and hypotensive actions. In agreement with results obtained with other beta-blockers, only the S-enantiomer of carvedilol exerts beta-blocking effects. In contrast, no substantial difference between the enantiomers could be seen with respect to alpha-blockade. The greater hypotensive activity of S-carvedilol may be attributed to beta-blockade, which inhibits counter-regulatory mechanisms provoked by vasodilation. From these results it is concluded that there is a rationale for using carvedilol as the racemate. Using the S-enantiomer would lead to relatively strong beta-blockade with only a weak vasodilating effect. The R-enantiomer alone would act only as a hypotensive agent without beta-blockade.
Bartsch
W
W
Department of Cardiovascular Research, Boehringer Mannheim GmbH, Federal Republic of Germany.
Sponer
G
G
Strein
K
K
Müller-Beckmann
B
B
Kling
L
L
Böhm
E
E
Martin
U
U
Borbe
H O
HO
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013237:Stereoisomerism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; D008729:Methoxamine; D007545:Isoproterenol