Dietary magnesium and migraine in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2001-2004.

BACKGROUND: Clinical trials have demonstrated magnesium supplements to be effective for prophylactic treatment of migraine. Dietary magnesium intake of many Americans is known to be below nutritional recommendations, but typical magnesium intake from dietary sources in adults with migraine has not previously been evaluated. OBJECTIVE: This study aimed to quantify dietary and total (diet + supplement) magnesium consumption of adults with migraine or severe headache in the United States, and to investigate the relationship between magnesium consumption levels and prevalence of migraine or severe headache. METHODS: This analysis included cross-sectional data from 3626 participants, 20- to 50-years old in the National Health and Nutrition Examination Survey between 2001 and 2004. Presence of migraine or severe headache in the past 3 months was determined by questionnaire. Individuals responding affirmatively were classified as having migraine, and individuals reporting not experiencing migraine or severe headache were classified as controls. Dietary magnesium intake was determined from a 24-hour recall interview, supplemental magnesium intake was determined from the dietary supplements interview, and total magnesium intake was the sum of dietary and supplement intake. RESULTS: Mean dietary consumption of magnesium was below the recommended dietary allowance (RDA) for both migraine (n = 905) and control groups (n = 2721). Attainment of the RDA through a combination of diet and supplements was associated with lower adjusted odds of migraine (odds ratio [OR] = 0.83, 95% confidence intervals [CIs] = 0.70, 0.99, p = 0.035). Magnesium consumption in the highest quartile (Q) was associated with lower odds of migraine than in the lowest Q for both dietary (OR = 0.76, 95% CI = 0.63, 0.92, p = 0.006) and total (OR = 0.78, 95% CI = 0.62, 0.99, p = 0.042) magnesium intake in adjusted models. CONCLUSION: These results suggest inadequate consumption of magnesium intake is associated with migraine in U.S. adults ages 20-50. Further prospective investigations are warranted to evaluate the role of dietary magnesium intake on migraine.

Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer's disease.

Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer's disease (AD). Following this approach, a new series of N'-(4-benzylpiperidin-/piperazin-/benzhydrylpiperazin-1-yl)alkylamine derivatives were designed, synthesized and biologically evaluated as inhibitors of cholinesterases (ChEs), amyloid-beta (Aß) self aggregation and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives strongly inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 values in the low-nanomolar range, and were clearly more potent than the reference compound donepezil in this regard. Among them, inhibitors 5h and 5k, strongly inhibited AChE, with IC50 value of 6.83nM and 2.13nM, respectively, and particularly, compound 5k was found to be highly selective for AChE (∼38-fold). Moreover, both kinetic analysis of AChE inhibition and the docking study suggested that 5k binds simultaneously to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit self-induced Aß1-42 aggregation at 25µM with percentage inhibition from ∼54% to 89% and specially compound 5k provided highest inhibition (88.81%). Also, the derivatives containing methoxy and hydroxy groups showed potent oxygen radical absorbance capacity (ORAC) ranging from 2.2- to 4.4-fold of the Trolox value. Furthermore, results of ADMET studies suggested that all compounds exhibited appropriate drug like properties. Taken together, these results suggest that 5k might be a promising lead compound for further AD drug development.

Synthesis and pharmacological evaluation of [(4-arylpiperazin-1-yl)-alkyl]-carbamic acid ethyl ester derivatives as potential anxiolytic agents.

On the basis of our earlier studies, a series of N-{4-[4-(aryl) piperazin-1-yl]-phenyl}-amine derivatives containing terminal carbamoyl fragment with alkyl spacer of different lengths (15-20) were synthesized as ligands, for 5-hydroxytryptamine-1A (5-HT(1A)) receptor. Molecular modeling studies were undertaken to explain the influence of spacer length on ligands affinity towards 5-HT(1A) receptor. Compound 19 showed all the specific interactions responsible for recognition. The protonated amine of the ligand forms an ionic hydrogen bond with the negatively charged Asp116 of transmembrane3 helix (TM3), while the carbamoyl moiety interacts with Asn386 and Tyr390 of TM7. The aryl group is involved in forming a CH-π interaction with Phe362. The strong interaction of compound 19 with 5-HT(1A) receptor in docking studies was confirmed by radio ligand binding studies. Compound 19 showed high affinity for the receptor (Ki = 0.018 nM). In vivo pharmacological testing of compound 19 (3 mg/kg body weight) showed increased open arm entries, as well as time spent in Elevated plus Maze test. Toxicological analysis also revealed no significant biochemical or morphological alterations in the vital organs of experimental animals. Furthermore our results suggest that these compounds share some pharmacological effects with established anxiolytics and might prove to be effective compounds for the treatment of anxiety.

Synthesis and pharmacological evaluation of new arylpiperazines N-[4-[4-(aryl) piperazine-1-yl]-phenyl]-amine derivatives: putative role of 5-HT1A receptors.

In an attempt to design novel 5-HT(1A) agonists/partial agonists, based on an arylpiperazine nucleus, a series of N-{4-[4-(aryl)piperazine-1-yl]-phenyl}-amine derivatives were synthesized and biologically tested. The anxiolytic effect of the compounds was investigated employing the Elevated plus Maze (EPM) task. On the basis of in vivo functional test, compound 1c (3mg/kg) and 4c (3mg/kg) induced significant increments in open arm entries and time on EPM as compared to Buspirone. The anxiolytic effects of compounds 1c and 4c were effectively antagonized by WAY-100635, a 5-HT(1A) receptor antagonist (0.5mg/kg). Furthermore, we have also evaluated the concentration of 5-HT in the brain tissue using HPLC with fluorescent detection. Our result showed that serotonin levels were significantly decreased by approximately 38% (p<0.001) and approximately 32% (p<0.001) after acute administration of compounds 1c and 4c, respectively. These findings suggest that the anxiolytic like activity of these new arylpiperazines is mediated via 5-HT(1A) receptors in the brain.