Inhibitory effect of harmane on morphine-dependent Guinea pig ileum

Ann N Y Acad Sci. 2003 Dec:1009:185-9. doi: 10.1196/annals.1304.022.

Abstract

Studies on the occurrence and properties of b-carbolines structurally related to harmala alkaloids have gained attention since it was hypothesized that some of these compounds play a role in processes of substance abuse and dependence. This study investigates the effects of harmane on naloxone-precipitated withdrawal syndrome in morphine-dependent guinea pig ileum. Segments of ilea from starved male guinea pigs were obtained and fixed at a resting tension of 1 g in an organ bath containing 10(-6) M morphine in Tyrode solution at 37 degrees C, which was bubbled with 95% O(2) and 5% CO(2). Tissues were incubated in 10(-6) M morphine containing Tyrode solution for 4 hours before harmane was added. Naloxone and harmane had no effect on naive ilea. Naloxone (10(-6) M) contracted morphine-dependent ilea. Harmane significantly inhibited the contractile response to naloxone in a dose-dependent manner (10(-7) M = 24%; 10(-6) M = 49.3%; 10(-5) = 70%). These results suggest that harmane may have beneficial effects on morphine withdrawal syndrome.

MeSH terms

  • Adrenergic alpha-Antagonists / metabolism
  • Adrenergic alpha-Antagonists / pharmacology
  • Analgesics, Opioid / metabolism
  • Animals
  • Guinea Pigs
  • Harmine / analogs & derivatives*
  • Harmine / metabolism*
  • Harmine / pharmacology*
  • Idazoxan / metabolism
  • Idazoxan / pharmacology
  • Ileum / drug effects*
  • In Vitro Techniques
  • Male
  • Morphine / metabolism
  • Morphine Dependence*
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Naloxone / metabolism
  • Narcotic Antagonists / metabolism
  • Substance Withdrawal Syndrome
  • Yohimbine / metabolism
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Yohimbine
  • Naloxone
  • Harmine
  • Morphine
  • harman
  • Idazoxan