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Related Experiment Videos

ACTH: a structure-activity study on pilocarpine-induced epilepsy.

G Croiset1, D De Wied

  • 1Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, Netherlands.

European Journal of Pharmacology
|December 15, 1992
PubMed
Summary

Adrenocorticotropic hormone (ACTH) fragments, specifically smaller ones like ACTH-(4-9), can reduce the severity of pilocarpine-induced epilepsy in rats. These fragments, lacking peripheral effects, show potential as anti-epileptic agents.

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Pharmacology

Background:

  • Pilocarpine administration in rats reliably induces epileptic symptoms.
  • The role of adrenocorticotropic hormone (ACTH) and its fragments in neurological conditions is an area of ongoing research.

Purpose of the Study:

  • To investigate the potential anti-epileptic effects of various ACTH fragments on pilocarpine-induced seizures in rats.
  • To identify specific ACTH sequences responsible for reducing epileptiform activity.

Main Methods:

  • Rats were administered pilocarpine intracerebroventricularly to induce epilepsy.
  • Different ACTH fragments (e.g., ACTH-(1-39), ACTH-(4-9), ACTH-(7-16)) were administered subcutaneously as pretreatment.
  • Seizure severity and the incidence of motor seizures were evaluated.

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Main Results:

  • Larger ACTH fragments (ACTH-(1-39), ACTH-(1-24), ACTH-(1-18), ACTH-(1-16), ACTH-(18-39)) showed no anti-epileptic activity.
  • Smaller ACTH fragments (ACTH-(4-9), ACTH-(4-10), ACTH-(4-10)(7D-Phe), ACTH-(7-16), Org2766) significantly reduced seizure severity and motor seizure incidence.
  • A narrow bell-shaped dose-response relationship was observed, with optimal activity at 10 micrograms/rat for most fragments.

Conclusions:

  • ACTH fragments lacking peripheral endocrine activity possess anti-epileptic properties against pilocarpine-induced seizures in rats.
  • The anti-epileptic activity is localized to the ACTH molecule's sequence 1-16, particularly within the 4-7 and 7-16 regions.
  • These findings suggest potential therapeutic applications for specific ACTH fragments in epilepsy management.