Cortisol response in MS patients treated with ACTH (1-13) and metenkephalin

L Burnazovic-Ristic, N Mulabegovic, M Rakanovic-Todic. Medical faculty, Institute of pharmacology and toxicology, Bosnia and Herzegovina

Enkorten is a non-steroid and non-interferon drug, which consists of two neuropeptide components: ACTH (1-13) and met-enkephalin. As a combination of two endogenous neuropeptide components, Enkorten modulates immunological processes with anti-inflammatory, analgesic, antipyretic and antioxidant effects without side effects related to steroid and non-steroid anti-inflammatory drugs. ACTH 1-13 exerts its actions through interactions with melanocortin receptors. Melanocortin receptor family is physiologically important class of receptors and a part of the superfamiliy of G protein (guanine binding regulatory proteins)-coupled receptors. To date, 5 melanocortin receptors MC1R to MC5R have been identified [i] . They have been shown to have a wide and varied distribution throughout the body, being found in the central nervous system (CNS), periphery and immune cells. Melanocortin peptides exert multiple effects upon the host, including anti-inflammatory and immunomodulatory effects, control of food intake and feed efficiency, metabolism, body weight, cardiovascular regulation and exocrine secretion. The melanocortin-2 receptor (MC-2R), also known as ACTH receptor, is selectively activated by adrenocorticotropic hormone ACTH 1-39 but not by other melanocortin peptides .

It was hypothesized whether the peptides such as ACTH 1-13 are able to induce steroidogenesis. The hypothesis was tested during the treatment of acute relapses of RRMS patients treated with novel anti-inflammatory/immunomodulatory drug combination. The cortisol circadian rhythm was analysed during acute relapse and after fulfilment of treatment.

The study results suggest that administration of ACTH (1-13) and met-enkephalin as novel treatment of autoimmune disorders does not cause side effect typical of corticotrophin therapy. The physiological influences of ACTH 1-39 on production and release of steroids by the adrenal cortex, their circadian variation, and stress-related fluctuations are mediated by MC2R. Due to the fact that alpha MSH related peptides bind to MC1, MC3, MC4 and MC5 and not to MC2 receptors of ACTH 1-39, its administration does not cause side effect typical of corticotrophin therapy.