Systemic pretreatment with hetanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting oplate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.
Ketanserin Pretreatment Reverses Alfentanil-induced Muscle Rigidity
Received from the Department of Anesthesiology, University of California, San Diego, School of Medicine and the Veterans Administration Medical Center, San Diego, California; and the Division of Preclinical Neuroscience and Endocrinology, Scripps Clinic and Research Foundation, La Jolla, California. Accepted for publication April 10, 1987. Supported in part by NIDA grant #04043 and Janssen Pharmaceutica. Presented in part at the annual meeting of the American Society of Anesthesiologists in Las Vegas, Nevada, on October 21, 1986.
- Views Icon Views
- Share Icon Share
- Search Site
Matthew B. Weinger, Elizabeth J. Cline, N. Ty Smith, George F. Koob; Ketanserin Pretreatment Reverses Alfentanil-induced Muscle Rigidity. Anesthesiology 1987; 67:348–354 doi: https://doi.org/10.1097/00000542-198709000-00012
Download citation file: