Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Neuropharmacology. 2011 Sep;61(3):364-81. doi: 10.1016/j.neuropharm.2011.01.017. Epub 2011 Jan 20.

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Behavior / drug effects*
  • Behavior, Animal / drug effects
  • Hallucinogens / chemistry
  • Hallucinogens / toxicity*
  • Humans
  • Lysergic Acid Diethylamide / chemistry
  • Lysergic Acid Diethylamide / toxicity
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Phenethylamines / chemistry
  • Phenethylamines / toxicity
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Psilocybin / chemistry
  • Psilocybin / toxicity
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / toxicity*
  • Serotonin Syndrome / chemically induced
  • Serotonin Syndrome / metabolism
  • Serotonin Uptake Inhibitors / toxicity
  • Synaptic Transmission / drug effects

Substances

  • Hallucinogens
  • Nerve Tissue Proteins
  • Phenethylamines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Psilocybin
  • Lysergic Acid Diethylamide