Stereoselectivity of the histamine H3-presynaptic autoreceptor

Eur J Pharmacol. 1985 Oct 29;117(1):109-14. doi: 10.1016/0014-2999(85)90478-9.


The effects of the enantiomers of two chiral analogues of histamine (alpha, N alpha-dimethylhistamine and N alpha-methyl-alpha-chloromethylhistamine) were studied at H3-autoreceptors modulating histamine release in rat brain slices. These compounds act as H3-receptor agonists, displaying a low potency relative to histamine (below 4%) but a pronounced stereoselectivity (ratio of 31 for the isomers of alpha, N alpha-dimethylhistamine and 183 for their halogenated analogues) was observed. The (+)isomers (corresponding to S-configurated L-histidine) were highly preferred at H3-receptors, whereas the (-)isomers were more potent at H2-receptors, no difference being observed at H1-receptors. In addition, no such stereoselectivity was observed for the two isomers of a chiral impromidine derivative: both Sopromidine and its S enantiomer acted as antagonists of histamine at H3-autoreceptors with similar potencies (Ki = 5.6 X 10(-8) M and 4.5 X 10(-8) M), whereas Sopromidine acted as an H2-receptor agonist and the S-enantiomer as an H2-receptor antagonist. Our results indicate that H3-autoreceptors are chemically stereoselective, with structural requirements different from those of H1- and H2-receptors.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects
  • Histamine Antagonists / pharmacology*
  • Histamine Release / drug effects
  • Ileum / drug effects
  • Imidazoles / pharmacology
  • Impromidine
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Rats
  • Rats, Inbred Strains
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H3
  • Receptors, Neurotransmitter / metabolism*
  • Stereoisomerism


  • Histamine Antagonists
  • Imidazoles
  • Receptors, Histamine
  • Receptors, Histamine H3
  • Receptors, Neurotransmitter
  • Impromidine