Selective beta-adrenoceptor partial agonist effects of pindolol and xamoterol on skeletal muscle assessed by plasma creatine kinase changes in healthy subjects.
1. The effects of selective beta-adrenoceptor partial agonist activity on plasma creatine kinase (CK) and skeletal muscle symptoms were studied in normal volunteers. 2. A drug with beta 1-selective partial agonist activity (xamoterol) and one with partial agonist activity acting mainly through beta 2-adrenoceptors (pindolol) were each given for 3 weeks in a randomised double-blind crossover study in 10 subjects. Five additional subjects received only one drug. Plasma CK levels were monitored during a baseline placebo run-in phase, the active treatment period and a placebo washout phase which continued until CK levels returned to baseline. 3. The degree of beta-adrenoceptor antagonism was determined by the inhibition of exercise-induced tachycardia and was similar for the two drug doses used. 4. During pindolol administration plasma CK levels rose compared with pretreatment baseline levels and with levels during xamoterol administration which did not rise. After pindolol was withdrawn CK levels reached higher peaks in some subjects after 1-5 days. 5. Muscle cramps were reported by five subjects during pindolol administration and by one of these subjects but to a lesser extent during xamoterol administration. 6. Pindolol may produce this effect, which was not seen with xamoterol, because of its specific beta 2-adrenoceptor partial agonist activity. Elevations in plasma CK produced by this type of drug or its withdrawal may cause confusion in the diagnosis of muscle disease or myocardial infarction unless the myocardial isoenzyme is measured.
Tomlinson
B
B
Department of Clinical Pharmacology, University College and Middlesex School of Medicine, London.
Cruickshank
J M
JM
Hayes
Y
Y
Renondin
J C
JC
Lui
J B
JB
Graham
B R
BR
Jones
A
A
Lewis
A D
AD
Prichard
B N
BN
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology*; D010869:Pindolol / Q000009:adverse effects / Q000494:pharmacology*; D011412:Propanolamines / Q000009:adverse effects / Q000494:pharmacology*; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D017307:Xamoterol; D010869:Pindolol; D003402:Creatine Kinase