Non-invasive evaluation of hemodynamic, tremorogenic and biochemical effects in response to beta-adrenoceptor stimulation.
1, 4, 12 and 24 micrograms SOM 1397 CL, a new beta 2-adrenergic bronchodilator, were administered by inhalation to 10 healthy volunteers in a double-blind, placebo-controlled, within-subject crossover study in order to assess circulatory, tremorogenic and biochemical effects. 1 microgram SOM 1397 CL did not cause any relevant changes in the measured parameters. After administration of 4 micrograms a slight but continuous increase in tremor amplitude and c-AMP was observed. The effects on hemodynamics and other laboratory values could be considered negligible. Overdoses of 12 and 24 micrograms resulted in a dose-dependent increase in systolic blood pressure, pulse rate, tremor amplitude, alpha-AMP and lactic acid, as well as in a decrease of diastolic blood pressure and potassium. These effects may be partly attributable to beta 2-receptor stimulation. The method described in this paper can be applied as a useful tool for determination of beta 2-adrenergic activity in healthy volunteers, independent of the conventional methods which are used to evaluate efficacy of bronchodilators by the degree of bronchial muscular relaxation.
Adamus
W S
WS
Department of Medicine, Boehringer Ingelheim KG, Ingelheim/Rhein, Federal Republic of Germany.
Jansen
U
U
Schilling
J C
JC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D009930:Organic Chemicals; D011188:Potassium / Q000097:blood; D011674:Pulse / Q000187:drug effects; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced*
D000318:Adrenergic beta-Agonists; D007773:Lactates; D009930:Organic Chemicals; C059512:SOM 1397CL; D000242:Cyclic AMP; D011188:Potassium