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ANESTHETIC PHARMACOLOGY

The Hypnotic and Analgesic Effects of 2-Bromomelatonin

Mohamed Naguib, MB BCh, MSc, FFARCSI, MD^*, Max T. Baker, PhD^*, Gilberto Spadoni, PhD, and Marc Gregerson, BS^*

Departments of Anesthesia, *University of Iowa College of Medicine, Iowa City, Iowa; and Institute of Medicinal Chemistry and Toxicology, University of Urbino, piazza Rinascimento, Italy

Address correspondence and reprint requests to Mohamed Naguib, MB, BCh, MSc, FFARCSI, MD, Department of Anesthesia-6JCP, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52242-1009. Address e-mail to mohamed-naguib{at}uiowa.edu

2-Bromomelatonin is an analog of melatonin with a higher melatonin receptor affinity. We tested the hypnotic and analgesic properties of 2-bromomelatonin and compared them with those of propofol. Sprague-Dawley rats were assigned to receive 2-bromomelatonin or propofol IV, or morphine intraperitoneally. Righting reflex and response to tail clamping were assessed. Both 2-bromomelatonin and propofol caused a dose-dependent increase in the percent of rats displaying loss of both the righting reflex and the response to tail clamping. 2-Bromomelatonin was comparable to propofol in terms of its rapid onset and short duration of hypnosis. The 50% effective dose (95% confidence interval) for loss of righting reflex for propofol and 2-bromomelatonin were 3.7 (3.4–4.0) and 38 (35–41) mg/kg, respectively. Corresponding values for loss of response to tail clamp were 2.9 (3.5–4.0) and 21 (15–30) mg/kg, respectively. 2-Bromomelatonin is approximately 6–10 times less potent than propofol depending on the end-point used. Intraperitoneal 30 mg/kg morphine did not affect the righting reflex, but resulted in loss of response to tail clamping in all animals. 2-Bromomelatonin can exert hypnotic and antinocifensive effects similar to that observed with propofol. Unlike propofol, the reduced nocifensive behavior persisted after the animals had regained their righting reflex. This study provides evidence that 2-bromomelatonin has properties that are desirable in anesthetics or anesthetic adjuvants.

IMPLICATIONS: The IV administration of 2-bromomelatonin can exert both hypnotic and antinocifensive effects.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999