N-Acetylserotonin vs Melatonin: In-Vitro Controlled Release from Hydrophilic Matrix Tablets

Abstract

Background: N-Acetylserotonin (NAS, N-acetyl-5-hydroxytryptamine) is the immediate precursor of the neurohormone melatonin (MT, N-acetyl-5-methoxytryptamine), which regulates sleep and wake cycles. NAS is produced by the N-acetylation of serotonin and is converted to melatonin via the action of Acetylserotonin O-methyltransferase (ASMT). Like melatonin, NAS acts as an agonist on the melatonin receptors MT1, MT2, and MT3. However, as NAS is abundant in specific brain areas, separate from serotonin and melatonin, it may also have discrete central effects. Indicatively, it has been reported that NAS may play a role in the antidepressant effects of Selective Serotonin Reuptake Inhibitors (SSRIs) and Monoamine Oxidase Inhibitors (MAOIs). </P><P> Objective: To decipher the controlled release characteristics of the active substances (NAS and MT) in a quick initial pace, aiming at a satisfactory sleep-onset related anti-depressive profile and prolonged release, thereafter, targeting at coping with poor sleep quality problems. </P><P> Methods: A series of hydrophilic matrix tablets involving as excipients, hydroxypropylmethylcellulose (HPMC) K15M, low viscosity sodium alginate, lactose monohydrate, and polyvinylpyrrolidone (PVP) M.W.: 10.000 and 55.000) was developed and tested at two dissolution media (pH 1.2 and 7.4). </P><P> Results: The results showed that commonly used excipients with different physicochemical properties govern the controlled release of NAS and MT from solid matrix systems. </P><P> Conclusions: We have demonstrated how broadly used excipients affect the in vitro controlled release of NAS and MT from solid pharmaceutical formulations. Currently, we extend our studies on the controlled release of these drugs using various other biopolymers/formulants of different physicochemical characteristics, which will help to highlight the discrete release profiles of NAS and MT.

A study of the mechanism of small-molecule soybean-protein-derived peptide supplement to promote sleep in a mouse model

“…15,16 MT is then synthesized from 5-HT in two steps: 5-HT is rst subjected to a reaction catalyzed by AANAT to form N-acetyl-5-hydroxytryptamine, which is then methylated using hydroxy hydrazine-oxygenmethyltransferase (ASMT) to obtain MT. 17,18 The MT synthesis route is summarized in Fig. 1.…”

Per Os Administered Modified-Release Solid Formulations of Melatonin: A Review of the Latest Developments Including the Design of Experiments (DoE) Approach

“…The objective was to produce a formulation with a quick initial pace, aiming at a satisfactory sleep onset, followed by a prolonged release that could target poor sleep quality problems. The dissolution results indicated that the combination of the excipients with different physicochemical properties could alter the release of MLT from solid matrix systems [9].…”

Melatonin Modified Release Formulations Designed for Sleep Disorders

“…One of the most common ways is the use of various excipients that facilitate the prolong release when tablet manufacturing [8][9][10][11][12][13]. These excipients usually involve hydroxypropylmethylcellulose, polyvinylpyrrolidone, and sodium alginate in various molecular weights or forms.…”