Advancements in neuroactive peptides in seizures

ABSTRACT

Introduction

Neuroactive peptides are peptides produced by neurons and released through controlled mechanisms that bind to specific receptors on nerve, glial, or other cell types, causing biochemical response(s) within these cells.

Areas covered

This article summarizes and interprets recent advancements in our knowledge of neuroactive peptides with pro- or anti-convulsant action, and about new drugs that use the molecular machinery of neuroactive peptides to suppress seizures.

Expert opinion

According to the results of preclinical and limited clinical investigations to date, the highest potential to become anti-epileptic drugs with marketing authorization belongs to non-peptide agonists of melanocortin receptors, thyrotropin-releasing hormone receptors, ghrelin receptors, galanin receptors, somatostatin and cortistatin receptors, oxytocin receptors, cholecystokinin receptors, and opioid kappa receptors, followed by non-peptide antagonists of the renin-angiotensin system, corticotropin-releasing hormone receptors, NK1 receptors for substance P, arginine-vasopressin receptors, and opioid delta receptors.

KEYWORDS:

• Epilepsy
• neuroactive peptides
• non-peptide agonists
• non-peptide antagonists

Article highlights

• Although there are more than 120 neuroactive peptides in the human brain, only 21 of them are involved in the development or modulation of seizures.

• Except for adrenocorticotropic hormone (ACTH) and thyrotropin releasing hormone (TRH), other neuroactive peptides and agonists or antagonists of their receptors are not yet used in clinical practice; just a few are tested in clinical studies, and the great majority are in the pre-clinical phase of development.

• Neuroactive peptides with anti-convulsant action are ACTH, TRH, ghrelin, galanin, somatostatin, cortistatin, oxytocin, cholecystokinin, and dynorphin.

• Neuroactive peptides with pro-convulsant action are angiotensins, corticotropin-releasing hormone, substance P, arginine-vasopressin, beta-endorphin, and enkephalins.

• There is an urgent need to develop new non-peptide agonists and antagonists of receptors for neuroactive peptides capable of crossing the blood-brain barrier after systemic administration.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was partially financially supported by Grant No 175007 given by Serbian Ministry of Education, Science and Technological Development.