Dactinomycin® Analogues as Neurokinin‐2 Receptor Antagonists

Abstract

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. 1993 Nordic Pharmacological Society