Hypoglycemia induced by intrathecal opioids in mice: stereospecificity, drug specificity and effect of fasting.

Abstract

The specificity of the hypoglycemic response to the intrathecal (i.t.) administration of the naturally occurring (-)-enantiomer of morphine previously reported from our laboratory was studied in mice. (+)-Morphine HBr (50 micrograms) caused a behavioral syndrome (scratching, biting, seizures) comparable to that produced by (-)-morphine sulfate (50 micrograms), but did not cause hypoglycemia. Many opioids, at a dose of 50 micrograms i.t. in nonfasted mice, showed either a saline-like hyperglycemic response or no significant effect on blood glucose. (+)-Morphine, ketocyclazocine, U-50,488, (-)- and (+)-N-allyl-normetazocine, beta-endorphin, (-)- and (+)-naloxone and naltrexone caused hyperglycemia. Significant changes from basal blood glucose were not produced by [D-Pen2, L-Pen5]-enkephalin, [D-Ser2]-Leu-enkephalin-Thr or sufentanil in 50-micrograms doses, or by codeine (300 micrograms), levorphanol (400 micrograms) or methadone (200-400 micrograms). Agonists which produced both hypoglycemic and behavioral effects were, in order of decreasing potency, hydromorphone greater than normorphine greater than morphine greater than 6-acetylmorphine greater than oxymorphone much greater than heroin. Morphine-induced hypoglycemia was partially antagonized by the i.t. coadministration of naloxone methobromide (10 micrograms). Fasting for 24 hr increased the sensitivity to hypoglycemic and lethal effects of morphine. D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (5-50 micrograms i.t.) tended to decrease blood glucose in both nonfasted and fasted mice, but these effects were moderate and appeared to be unrelated to dose.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: D A Brase, A K Singha, U Estrada, F Lux, W L Dewey
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 253 Issue 3 Pg. 899-904 (Jun 1990) ISSN: 0022-3565 [Print] United States
• PMID: 2359029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Morphine Derivatives
• Morphine

Topics

• Animals
• Blood Glucose
• Dose-Response Relationship, Drug
• Fasting (metabolism)
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (pharmacology)
• Injections, Spinal
• Male
• Mice
• Mice, Inbred ICR
• Morphine (pharmacology)
• Morphine Derivatives (pharmacology)
• Stereoisomerism