The analgesic tropane analogue (+/-)-SM 21 has a high affinity for sigma2 receptors

Life Sci. 1999;64(10):PL131-7. doi: 10.1016/s0024-3205(99)00014-4.

Abstract

The analgesic properties of the tropane analogue (+/-)-SM 21 have been attributed to the antagonism of presynaptic m2 receptors resulting in a potentiation of acetylcholine release. However, drugs targeting a number of other neurotransmitter receptors have been shown to enhance acetylcholine release. In the current study, in vitro studies were conducted in order to determine the affinity of (+/-)-SM 21 for serotonin 5-HT3, 5-HT4, and sigma receptors. Our results indicate that (+/-)-SM 21, and its structural congeners, have a relatively high affinity for sigma2 receptors relative to their reported affinity for muscarinic receptors. The higher affinity for sigma2 versus sigma1 receptors indicates that (+/-)-SM 21 may be a suitable lead compound for developing sigma2-selective ligands.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / chemistry
  • Analgesics / metabolism*
  • Animals
  • Atropine / chemistry
  • Atropine / metabolism
  • Benzimidazoles / chemistry
  • Benzimidazoles / metabolism
  • Benztropine / chemistry
  • Benztropine / metabolism
  • Binding, Competitive
  • Brain / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / metabolism
  • Butyrates / chemistry
  • Butyrates / metabolism*
  • Guinea Pigs
  • In Vitro Techniques
  • Ligands
  • Muscarinic Antagonists / chemistry
  • Muscarinic Antagonists / metabolism
  • Rats
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT3
  • Receptors, Serotonin, 5-HT4
  • Receptors, sigma / metabolism*
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / metabolism
  • Sigma-1 Receptor
  • Structure-Activity Relationship
  • Tropanes / chemistry
  • Tropanes / metabolism*

Substances

  • Analgesics
  • Benzimidazoles
  • Bridged Bicyclo Compounds, Heterocyclic
  • Butyrates
  • Ligands
  • Muscarinic Antagonists
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Receptors, sigma
  • Serotonin Antagonists
  • Tropanes
  • sigma-2 receptor
  • (endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide
  • SM 21
  • Receptors, Serotonin, 5-HT4
  • Benztropine
  • Atropine
  • bemesetron