Ampullosporin A, a peptaibol from Sepedonium ampullosporum HKI-0053 with neuroleptic-like activity

Behav Brain Res. 2009 Nov 5;203(2):232-9. doi: 10.1016/j.bbr.2009.05.012. Epub 2009 May 18.

Abstract

The potential neuroleptic-like effect of ampullosporin A, a new peptaibol, isolated from the fungus Sepedonium ampullosporum HKI-0053, was characterized using specific behavioural models and methods. Ampullosporin A (amp) disrupted the retrieval of a well-trained conditioned reaction and normalized the behavioural effects of subchronic ketamine treatment in the social interaction test in a dose which showed only inconsiderable side effects. The experiments demonstrated that the substance did not antagonize the apomorphine (apo) induced hyperactivity. On the other hand, the locomotor stimulation induced by the NMDA receptor antagonist MK-801 was nearly completely suppressed by ampullosporin A, supposing interactions with the glutamatergic system. Binding studies demonstrated no interaction with dopaminergic D(1) and D(2) receptors. However, amp can alter the activity of glutamate receptors. The results resemble characteristics of an atypical neuroleptic drug. But further experiments are necessary to validate the suggested neuroleptic-like activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology
  • Anxiety / chemically induced
  • Apomorphine / pharmacology
  • Avoidance Learning / drug effects
  • Body Temperature / drug effects
  • Brain / metabolism
  • Catalepsy / chemically induced
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism
  • Glutamic Acid / metabolism
  • Hyperkinesis / chemically induced
  • Hyperkinesis / metabolism
  • Male
  • Motor Activity / drug effects
  • Peptaibols
  • Peptides / adverse effects
  • Peptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Rotarod Performance Test
  • Social Behavior

Substances

  • Antipsychotic Agents
  • Peptaibols
  • Peptides
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, N-Methyl-D-Aspartate
  • ampullosporin
  • Glutamic Acid
  • Dizocilpine Maleate
  • Apomorphine
  • Dopamine