Plasma concentrations of tris(1-chloro-2-propyl) phosphate and a metabolite b in Sprague-Dawley rats and B6C3F1/N mice from a chronic study of tris(chloropropyl) phosphate via feed.

Tris(chloropropyl) phosphate (TCPP) is an organophosphorus flame retardant and plasticizer used in manufacturing and multiple consumer products. Commercial TCPP is a ubiquitous environmental contaminant and TCPP or its metabolites have been detected in human plasma and urine. In response to the demonstrated widespread human exposure and lack of toxicity data, the Division of the National Toxicology Program is investigating the chronic toxicity of TCPP following perinatal exposure in HSD:Sprague Dawley®SD® (HSD) rats (up to 20,000 ppm) and adult exposure in B6C3F1/N mice (females, up to 10,000 ppm; males up to 5000 ppm) to TCPP via feed.

Mammalian exocrine secretions XIX. Chemical characterization of the interdigital secretion of the Black Wildebeest, Connochaetes gnou.

Using gas chromatography (GC) in conjunction with electron impact mass spectrometry and retention-time comparison, 94 compounds, ranging from 2-methyl-2-propenal to octadecanoic acid, were identified in the interdigital secretions of male and female black wildebeests, Connochaetes gnou (also known as the white-tailed gnu). The constituents of these secretions belong to many different compound classes, including hydrocarbons, alcohols, aromatics and aliphatic carbonyl compounds including carboxylic acids as well as carboxylic acid esters. Relatively small quantitative differences were found between the male and female interdigital secretions.

Effects of Intranasal Epinephrine on Cerebrospinal Fluid Epinephrine Pharmacokinetics, Nasal Mucosa, Plasma Epinephrine Pharmacokinetics, and Cardiovascular Changes.

Purpose: We aimed to assess intranasal (IN) epinephrine effects on cerebrospinal fluid (CSF) absorption, nasal mucosa quality, plasma epinephrine pharmacokinetics (PK), and cardiovascular changes in dogs.

Methods: CSF epinephrine concentration was measured and nasal mucosa quality was evaluated after IN epinephrine 4 mg and one or two 4 mg doses (21 min apart), respectively. Maximum plasma concentration [C], time to C [T], area under the curve from 0 to 120 min [AUC], and cardiovascular effects were evaluated after epinephrine IN (4 and 5 mg) and intramuscular (IM; 0.

Intranasal epinephrine in dogs: Pharmacokinetic and heart rate effects.

Epinephrine is the standard of care for the treatment of severe allergy and anaphylaxis. Epinephrine is most often administered through the intramuscular (IM) route via autoinjector. The current study aimed to evaluate an alternative method of epinephrine treatment through intranasal (IN) delivery in dogs.

Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model.

Background: Histamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine.

Methods: Dogs received 5% histamine or saline IN followed by 4 mg epinephrine IN.

Bioactive products from singlet oxygen photooxygenation of cannabinoids.

Photooxygenation of Δ tetrahydrocannabinol (Δ-THC), Δ tetrahydrocannabinol (Δ-THC), Δ tetrahydrocannabinolic acid (Δ-THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides. Testing these compounds for their modulatory effect on cannabinoid receptors CB and CB led to the identification of 7 and 21 as CB partial agonists with Ki values of 0.043 μM and 0.

Minor oxygenated cannabinoids from high potency Cannabis sativa L.

Nine oxygenated cannabinoids were isolated from a high potency Cannabis sativa L. variety. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR, HRMS and GC-MS.

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.

Evaluation of Phytocannabinoids from High Potency using Bioassays to Determine Structure-Activity Relationships for Cannabinoid Receptor 1 and Cannabinoid Receptor 2.

has been around for thousands of years and has been used recreationally, medicinally, and for fiber. Over 500 compounds have been isolated from with approximately 105 being cannabinoids. Of those 105 compounds, Δ-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with .

Cannabisol, a novel Δ-THC dimer possessing a unique methylene bridge, isolated from .

Cannabisol (), a unique dimer of Δ-tetrahydrocannabinol (Δ-THC) with a methylene bridge, was isolated from . This is the first example of a C-bridged dimeric cannabinoid. The structure of was unambiguously deduced by HRESIMS, GCMS, and NMR spectroscopy.

Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008.

The University of Mississippi has a contract with the National Institute on Drug Abuse (NIDA) to carry out a variety of research activities dealing with cannabis, including the Potency Monitoring (PM) program, which provides analytical potency data on cannabis preparations confiscated in the United States. This report provides data on 46,211 samples seized and analyzed by gas chromatography-flame ionization detection (GC-FID) during 1993-2008. The data showed an upward trend in the mean Δ(9)-tetrahydrocannabinol (Δ(9)-THC) content of all confiscated cannabis preparations, which increased from 3.

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.

Microbial metabolism of cannflavin A and B isolated from Cannabis sativa.

Microbial metabolism of cannflavin A (1) and B (2), two biologically active flavonoids isolated from Cannabis sativa L., produced five metabolites (3-7). Incubation of 1 and 2 with Mucor ramannianus (ATCC 9628) and Beauveria bassiana (ATCC 13144), respectively, yielded 6''S,7''-dihydroxycannflavin A (3), 6''S,7''-dihydroxycannflavin A 7-sulfate (4) and 6''S,7''-dihydroxycannflavin A 4'-O-alpha-L-rhamnopyranoside (5), and cannflavin B 7-O-beta-D-4'''-O-methylglucopyranoside (6) and cannflavin B 7-sulfate (7), respectively.

An update on the synthesis and antibacterial effects of carbapenems.

The double-edged sword of antibiotic use in the fight against disease has saved countless lives at the cost of an escalation in pathogenic bacteria with increased resistance to multiple antibiotic classes. Reduction of resistance is a complicated multi-step endeavor that requires a sustained international effort of reduced utilization, infection control and development of effective and economical antimicrobial agents. The carbapenems are beta-lactam antibiotics that are stable to most beta-lactamases.

Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers.

Nine dihydroartemisinin acetal dimers (6-14) with diversely functionalized linker units were synthesized and tested for in vitro antiprotozoal, anticancer and antimicrobial activity. Compounds 6, 7 and 11 [IC(50): 3.0-6.

Structure determination and absolute configuration of cannabichromanone derivatives from high potency Cannabis sativa.

Three new cannabichromanone derivatives were isolated from high potency cannabis, along with the known cannabichromanone. Full spectroscopic data, including the use of electronic circular dichroism and Mosher ester analysis to determine the absolute configuration of these compounds, are reported. All isolates were tested for antimicrobial, antimalarial, antileishmanial and anti-oxidant activity.

Artemisinin dimer anticancer activity correlates with heme-catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction.

Analogs of the malaria therapeutic, artemisinin, possess in vitro and in vivo anticancer activity. In this study, two dimeric artemisinins (NSC724910 and 735847) were studied to determine their mechanism of action. Dimers were >1,000 fold more active than monomer and treatment was associated with increased reactive oxygen species (ROS) and apoptosis induction.

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.

Biologically active cannabinoids from high-potency Cannabis sativa.

Nine new cannabinoids (1-9) were isolated from a high-potency variety of Cannabis sativa. Their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3''-hydroxy-Delta((4'',5''))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7R-cannabicoumarononic acid A (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid A (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) through 1D and 2D NMR spectroscopy, GC-MS, and HRESIMS. The known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6'-acetate was isolated for the first time from cannabis.

Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity.

Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 microM (most active).

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.

Cannabinoid ester constituents from high-potency Cannabis sativa.

Eleven new cannabinoid esters, together with three known cannabinoid acids and Delta9-tetrahydrocannabinol ( Delta9-THC ), were isolated from a high-potency variety of Cannabis sativa. The structures were determined by extensive spectroscopic analyses to be beta-fenchyl Delta9-tetrahydrocannabinolate ( 1), epi-bornyl Delta9-tetrahydrocannabinolate ( 2), alpha-terpenyl Delta9-tetrahydrocannabinolate ( 3), 4-terpenyl Delta 9-tetrahydrocannabinolate ( 4), alpha-cadinyl Delta9-tetrahydrocannabinolate ( 5), gamma-eudesmyl Delta9-tetrahydrocannabinolate ( 6), gamma-eudesmyl cannabigerolate ( 7), 4-terpenyl cannabinolate ( 8), bornyl Delta9-tetrahydrocannabinolate ( 9), alpha-fenchyl Delta9-tetrahydrocannabinolate ( 10), alpha-cadinyl cannabigerolate ( 11), Delta9-tetrahydrocannabinol ( Delta9-THC ), Delta9-tetrahydrocannabinolic acid A ( Delta9-THCA ), cannabinolic acid A ( CBNA), and cannabigerolic acid ( CBGA). Compound 8 showed moderate antimicrobial activity against Candida albicans ATCC 90028 with an IC 50 value of 8.

Isolation and characterization of new Cannabis constituents from a high potency variety.

Phytochemical investigation of a high potency variety of Cannabis sativa L. resulted in the isolation of six new metabolites, (+/-)-6,7-trans-epoxycannabigerolic acid ( 2), (+/-)-6,7- CIS-epoxycannabigerolic acid ( 3), (+/-)-6,7- CIS-epoxycannabigerol ( 4), (+/-)-6,7-trans-epoxycannabigerol ( 5), 5'-methyl-4-pentylbiphenyl-2,2',6-triol ( 7), and 7-methoxycannabispirone ( 8), along with seven known compounds namely, cannabigerolic acid ( 1), 5'-methoxycannabigerolic acid ( 6), cannabispirone ( 9), beta-cannabispiranol ( 10), dehydrocannabifuran ( 11), cannflavin B ( 12) and cannabigerol ( 13). The antimicrobial as well as the antileishmanial activities were investigated.

Bioactive constituents from Turkish Pimpinella species.

A new 'phenylpropanoid', 4-(3-methyloxiran-2-yl)phenyl 2-methylbutanoate (1), a new trinorsesquiterpene, 4-(6-methylbicyclo[4.1.0]hept-2-en-7-yl)butan-2-one (2), and eight known compounds (3-10) were isolated from the essential oils of several Pimpinella species growing in Turkey.