BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by L-NAME/thiopental combination

Inflammopharmacology. 2015 Dec;23(6):329-36. doi: 10.1007/s10787-015-0249-9. Epub 2015 Nov 13.

Abstract

Aim: We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157.

Main methods: (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 μg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental.

Key findings: (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 μg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats.

Significance: Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157).

Keywords: Anaesthesia; BPC 157; Rats; Thiopental.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia / methods
  • Anesthetics, General / pharmacology*
  • Animals
  • Anti-Ulcer Agents / pharmacology
  • Arginine / metabolism
  • Drug Synergism
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Peptide Fragments / pharmacology*
  • Proteins / pharmacology*
  • Rats
  • Rats, Wistar
  • Thiopental / pharmacology*

Substances

  • Anesthetics, General
  • Anti-Ulcer Agents
  • Peptide Fragments
  • Proteins
  • BPC 157
  • Arginine
  • Thiopental
  • NG-Nitroarginine Methyl Ester