Phenolic compounds from nutmeg (Myristica fragrans Houtt.) inhibit the endocannabinoid-modulating enzyme fatty acid amide hydrolase.

Objectives: The study aimed to identify nutmeg compounds that indirectly interact with the endocannabinoid system through inhibition of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes.

Methods: Thirteen compounds were screened for FAAH and MAGL inhibition. Compounds demonstrating significant FAAH inhibition were evaluated to determine the halfmaximal inhibitory concentration (IC ).

Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space.

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo-,-dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1-indol-3-yl)-,-dimethylethanamine scaffold with different halogen substitutions.

Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg ( Houtt.).

Nutmeg is a valued kitchen spice that has been used for centuries all over the world. In addition to its use in flavoring foods and beverages, nutmeg has been used in traditional remedies for stomach and kidney disorders. The antioxidant, antimicrobial and central nervous system effects of nutmeg have also been reported in literature.

Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract.

Context: Nutmeg [Myristica fragrans Houtt. (Myristicaceae)] has a long-standing reputation of psychoactivity. Anecdotal reports of nutmeg use as a cheap marijuana substitute, coupled to previous studies reporting a cannabimimetic-like action, suggest that nutmeg may interact with the endocannabinoid system.

Review of available studies of the neurobiology and pharmacotherapeutic management of trichotillomania.

Trichotillomania (TTM) is a psychiatric disorder characterized by an irresistible urge to pull out one's hair. Currently there are no FDA approved treatments for TTM, which makes it difficult for clinicians to select an appropriate therapeutic plan. The clinical studies that have been performed do not provide sufficient or consistent evidence regarding which drug classes should be administered.

Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa.

Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied.

Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation.

Pterostilbene, a natural analog of resveratrol, has diverse health-beneficial properties. However, the neurological activities of this compound are largely unexplored. Here, we report that pterostilbene shows anxiolytic-like actions by down-regulating phosphorylated levels of extracellular regulated kinases in the hippocampus of mice.

Neurobehavioral and transcriptional effects of acrylamide in juvenile rats.

Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in juvenile rats.

Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy.

Towards a better understanding of the psychopharmacology of nutmeg: Activities in the mouse tetrad assay.

Ethnopharmacological Relevance: Nutmeg, the seeds of Myritica fragrans (family Myristicaceae), is a well known kitchen spice with a long-standing reputation as a psychoactive herb. Nutmeg at high doses is considered a cheap substitute to several drugs of abuse. Earlier reports have attributed amphetamine-like activities to nutmeg.

Naturally occurring and related synthetic cannabinoids and their potential therapeutic applications.

Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa L. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to Delta(9)-THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune and endocrine systems.

Non-cannabinoid constituents from a high potency Cannabis sativa variety.

Six new non-cannabinoid constituents were isolated from a high potency Cannabis sativa L. variety, namely 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone (1), 4,5-dihydroxy-2,3,6-trimethoxy-9,10-dihydrophenanthrene (2), 4-hydroxy-2,3,6,7-tetramethoxy-9,10-dihydrophenanthrene (3), 4,7-dimethoxy-1,2,5-trihydroxyphenanthrene (4), cannflavin C (5) and beta-sitosteryl-3-O-beta-d-glucopyranoside-2'-O-palmitate (6). In addition, five known compounds, alpha-cannabispiranol (7), chrysoeriol (8), 6-prenylapigenin (9), cannflavin A (10) and beta-acetyl cannabispiranol (11) were identified, with 8 and 9 being reported for the first time from cannabis.

Amelioration of the cardiovascular manifestations of the yellow scorpion Leiurus quinquestriatus envenomation in rats by red grape seeds proanthocyanidins.

The study attempts to determine the involvement of oxidative stress in cardiovascular manifestations during Leiurus quinquestriatus quinquestriatus (LQQ) scorpion envenomation and to examine the possible protective role of red grape seed proanthocyanidins (GSP) against such effects. Lethality studies conducted in mice demonstrated a significant (p<0.01) protection of GSP against venom lethality.

Protective effect of red grape seeds proanthocyanidins against induction of diabetes by alloxan in rats.

It has been documented that impaired homeostasis in diabetes mellitus is associated with increased production of reactive oxygen species and depletion of the antioxidant defense systems. Natural grape seed proanthocyanidins (GSP) are potent free radical scavengers and hence provide significant protection against oxidative stress. Accordingly, the present study focused on investigating the possible protective role of GSP against free radical-mediated damage in pancreatic tissues of alloxan-induced diabetes in rats.

Synthesis and pharmacological screening for muscle relaxant, anticonvulsant, and sedative activities of certain organic compounds produced by Michael addition.

Michael addition of certain nucleophiles on alpha, beta-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with alpha-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17.

Ephedra in perspective--a current review.

Although the traditional use of Ephedra 'ma huang' has been established for thousands of years, its resurgence in the US as a herbal dietary supplement is currently a matter of national controversy. At the heart of the debate are three important questions: (1) the identity and composition of Ephedra products with regard to ephedrine and related alkaloids; (2) the potential therapeutic utility of Ephedra supplements for weight loss or performance enhancement; and (3) potential health risks associated with such uses of Ephedra, particularly in sensitive individuals or in cases of intentional abuse for its stimulant properties. This review surveys the literature on Ephedra with regard to traditional uses, botany, chemistry, analytics, pharmacological effects and health risks.

Gender differences in the effect of salinity on aldicarb uptake, elimination, and in vitro metabolism in Japanese medaka, Oryzias latipes.

Toxicity studies have shown that salinity enhances the toxicity of aldicarb to female Japanese medaka. Although previous studies indicated that biotransformation may be important in these effects, other dispositional factors may play a role in this scenario. Male and female medaka were separately acclimated to three salinity regimens: 1.

Effect of 17beta-estradiol and testosterone on the expression of flavin-containing monooxygenase and the toxicity of aldicarb to Japanese medaka, Oryzias latipes.

Previous studies in our laboratory indicated gender differences in salinity-enhanced acute toxicity of aldicarb in Japanese medaka with females being more susceptible. In the current study, the effects of the sex steroids, 17beta estradiol (E2) and testosterone (T) on aldicarb toxicity was examined. Adult Japanese medaka were separated by sex and exposed to 100 microg/l E2 or T for 6 days followed by exposure to the 96-h LC50 (0.