Dactinomycin analogues as neurokinin-2 receptor antagonists

Pharmacol Toxicol. 1993 Dec;73(6):311-4. doi: 10.1111/j.1600-0773.1993.tb01357.x.

Abstract

Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor antagonist in addition to its inhibiting action on DNA replication. We investigated in the isolated guinea-pig bronchi the action of 3 Dactinomycin analogues on the contractions evoked by the selective neurokinin-2 receptor agonist [Nle10] neurokinin A(4-10). These analogues included 4,4'-Gly-Dactinomycin and the single peptide lactone of dactinomycin which are inactive on DNA replication and 5,5'-MeLeu-Dactinomycin, which has potent antitumour activity. Independently of their known effect on DNA replication, the three analogues showed neurokinin-2 antagonistic activity which was lower than for Dactinomycin.

Publication types

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

MeSH terms

  • Animals
  • Bronchi / drug effects
  • DNA Replication / drug effects
  • Dactinomycin / analogs & derivatives
  • Dactinomycin / pharmacology*
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Receptors, Neurokinin-2 / antagonists & inhibitors*

Substances

  • Receptors, Neurokinin-2
  • Dactinomycin