Differential pharmacological effects of antimuscarinic drugs on heart rate: a randomized, placebo-controlled, double-blind, crossover study with tolterodine and darifenacin in healthy participants > or = 50 years.
Antimuscarinics, used commonly to treat overactive bladder, may differ in their potential to increase heart rate via effects on cardiac muscarinic M2 receptors. This prospective, 3-way crossover, randomized, double-blind study assessed the heart rate effects of 7 days' exposure to a nonselective M2/M3 receptor blocker (tolterodine; 4 mg/d), a highly selective M3 receptor blocker (darifenacin; 15 mg/d), and placebo in 162 healthy participants > or = 50 years. Heart rate was measured by 24-hour Holter monitoring. Tolterodine significantly increased heart rate versus darifenacin and heart rate versus placebo, while darifenacin did not affect heart rate versus placebo. The proportion of participants with an increase in mean heart rate per 24 hours of > or =5 beats per minute was higher with tolterodine than with darifenacin (P = .0004) or with placebo (P = .0114) but did not differ between darifenacin and placebo. The results show that antimuscarinics exert differential effects on heart rate depending on their muscarinic receptor profile. This should be considered when selecting a treatment.
Olshansky
Brian
B
University of Iowa Hospitals, Iowa City, Iowa 52242, USA. brian-olshansky@uiowa.edu
Ebinger
Ursula
U
Brum
José
J
Egermark
Mathias
M
Viegas
Andrea
A
Rekeda
Ludmyla
L
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology*; D001572:Benzofurans / Q000009:adverse effects / Q000494:pharmacology*; D003248:Constipation / Q000139:chemically induced; D003408:Cresols / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000009:adverse effects / Q000494:pharmacology*; D011446:Prospective Studies; D011759:Pyrrolidines / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D000068737:Tolterodine Tartrate; D014987:Xerostomia / Q000139:chemically induced
D001559:Benzhydryl Compounds; D001572:Benzofurans; D003408:Cresols; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C101207:darifenacin