Quantitation of tremor in response to beta-adrenergic receptor stimulation in primates: relationship with hypokalemia.
The primary adverse effect of stimulation of beta2-adrenergic receptors is elicitation of tremor. Tremor measurements in response to beta2-adrenergic receptor stimulation were performed in a quantitative manner using a modified miniature semiconductor accelerometer in African green monkeys. The accelerometer was taped to the middle finger tip of anesthetized monkeys, and recordings of onset, duration and peak tremor responses were obtained. The selective beta2-adrenergic agonist, salbutamol (0.5 mg/kg i.v.), caused a marked increase in tremor which started within 5 min following injection and lasted for approximately 60 min. The finger tremor response was not visible, but was measurable by the accelerometer, and the increase in tremor was significantly greater from baseline within 10 min. Plasma K+ concentrations were markedly decreased within the first 15 min and remained at low steady-state concentrations during the 60-min recordings. The tremor response was abolished by the selective beta2-adrenergic receptor antagonist, ICI-118551 (0.2 mg/kg). ICI-118551 caused a significant reversal of the plasma K+ decrease but the K+ levels remained higher than control levels. These studies demonstrate that stimulation of beta2-adrenergic receptors causes tremor, most likely from entry of K+ into skeletal muscle and that there is a direct correlation between tremor and hypokalemic response.
Tesfamariam
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B
Department of Metabolic Diseases, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA.
Waldron
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T
Seymour
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AA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002522:Chlorocebus aethiops; D004347:Drug Interactions; D007702:Kinetocardiography; D011188:Potassium / Q000097:blood*; D011412:Propanolamines / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C026777:ICI 118551; D000420:Albuterol; D011188:Potassium