Age and beta-adrenergic receptor sensitivity to S(-)- and R,S(+/-)-propranolol in humans.
The relationship between age and beta-adrenergic receptor sensitivity to the pharmacologically active S(-) enantiomer and the racemic mixture of propranolol was evaluated in 46 healthy male subjects (age range, 24 to 89 years). The in vivo apparent dissociation constants for S(-)- and R,S(+/-)-propranolol were determined on the basis of the unbound steady-state plasma concentration of each and the dose of isoproterenol needed to increase the heart rate of the subjects by 25 beats/min in the absence (I25) and then in the presence of a continuous propranolol infusion. The I25 was significantly correlated with age (r = 0.700, p less than 0.05). The apparent dissociation constant for S(-)- and R,S(+/-)-propranolol demonstrated a significant, although weak, increase with advancing age (r = 0.403 and r = 0.396, respectively; p less than 0.05). Although these findings confirm those of other studies, beta-receptor sensitivity to propranolol was only modestly decreased with age in this study.
Colangelo
P M
PM
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Blouin
R A
RA
Steinmetz
J E
JE
McNamara
P J
PJ
DeMaria
A N
AN
Wedlund
P J
PJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012044:Regression Analysis; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol