Beta-adrenergic receptors in the elderly are not less sensitive to timolol.
The elderly have been reported to be less sensitive to the beta-adrenergic blocking effect of propranolol. However, propranolol is a racemate, and age-related changes in stereoselective metabolism or protein binding could confound interpretation of the data. To avoid these problems, we studied timolol in 12 young and 12 elderly healthy subjects. The dose of isoproterenol required for a heart rate increase of 25 bpm (I25) was determined before and 2 hours after an oral 10 mg dose of timolol. A dose ratio (DR) was calculated for each subject as the I25 after timolol/I25 before timolol. The binding constant for timolol binding to the receptor was calculated as the plasma timolol concentration divided by (DR-1). The I25 for the elderly group was significantly greater than the I25 for the young group, but the timolol binding constant was the same for both groups. We conclude that, although the elderly are less sensitive to isoproterenol, they are not less sensitive to timolol, and thus our data do not implicate a change in the interaction of beta-adrenoceptors with antagonists.
D000328:Adult; D000368:Aged; D000375:Aging; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013999:Timolol / Q000378:metabolism* / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D013999:Timolol; D007545:Isoproterenol