Rauvolfia vomitoria phytochemicals as promising sleep disorder agents targeting serotonin and adenosine receptors: An In-silico approach

Abstract

It is estimated that more than 30% of adults have insomnia symptoms, 10 -15% have daytime impairments such as fatigue, sleepiness, etc. and about 6-10% have insomnia disorder symptoms. The function of serotonin (5-hydroxytryptamine, 5-HT) and adenosine in the production of sleep is well-documented. 5-HT2A receptor antagonism and Adenosine A2A receptor agonism have been mechanism of action of some of the drugs used in the treatment of sleep disorders. Rauvolfia vomitoria Afzel has been reported to contain phytochemicalswith sedative and anti-convulsant properties.The compounds responsible for its sedative property is not known hence, this study is set to identify the compounds using in silico method as well as check the ADMET profile of the compounds. From the result, didodecylphthalate, oxalic acid allyl pentadecyl ester, vitamin E, and eicosanoic acid have better docking score (Kcal/mol) of -12, -10.58, -10.73, and -10.20 respectively with 5-HT2A receptors compared with the standard, aripiprazole, a known antagonist of the receptor, with docking score of -10.10 while 2Formy9[beta-d-ribofuranosyl] hypoxanthine, Elemol, Mandelic acid, and Trimebutine, had better docking score of -10.15, -8.07, -7.96 and -7.81 respectively with the adenosine A2A receptor compared to the standard, UKA, a known agonist, with score of -7.82. ADMET profiling revealed the compounds are safe as regards AMES toxicity, drug-induced liver injury and hERG blockers among others. The docking score, binding energy, ligand interaction, and ADMET profiling corroborate the claims thatR. vomitoriapossess a sedative effect.