Cannabinoids, including delta 9-tetrahydrocannabinol (THC), bind to receptors that couple to Gi/o-proteins and inhibit adenylyl cyclase. However, like other G-protein-coupled receptors, cannabinoid receptors are also coupled to other effector systems. This review examines the characteristics of the cannabinoid-G-protein-adenylyl cyclase system, and explores the role of cyclic AMP in mediating...
The purpose of this study was to investigate whether anandamide induces cannabimimetic responses, mainly mobilization of arachidonic acid, in primary cultures of rat brain cortical astrocytes. Confluent monolayer cultures of astrocytes, prelabeled with [3H]arachidonic acid, were incubated with anandamide or delta9-tetrahydrocannabinol (delta9-THC) in the presence or absence of thimerosal, a...
3,4-Methylenedioxymethamphetamine (MDMA) affects both dopamine and serotonin (5-HT) systems. One of its acute actions is to cause a reversible fall in steady-state brain 5-HT concentrations. To investigate the chemical basis of this acute effect, the brain levels of the parent compound and three major metabolites, 3,4- 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (DHMA) and...
To elucidate the psychotropic actions of calcium (Ca) antagonists, we investigated the effect of the voltage-dependent Ca channel antagonists, nifedipine and flunarizine, on phencyclidine (PCP)-induced changes in the monoamine metabolism in the regional brain areas of rats. The results indicate that the administration of nifedipine alone attenuated dopamine (DA) metabolism in the nucleus...
A concentration-related stimulation of anandamide (arachidonylethanolamide) synthesis by delta 9-tetrahydrocannabinol (THC) was observed in N-18TG2 neuroblastoma cells. Anandamide was detected and measured using an approach in which [3H]arachidonic acid and [14C]ethanolamine were incorporated into the phospholipids of subconfluent monolayers of cells, and the radiolabeled products were analyzed...
The exposure of cells in culture to cannabinoids results in a rapid and significant mobilization of phospholipid bound arachidonic acid. In vivo, this effect has been observed as a rise in eicosanoid tissue levels that may account for some of the pharmacological actions of delta 9-tetrahydrocannabinol (THC), the major psychoactive cannabinoid. Fluoroaluminate pretreatment of mouse peritoneal...
The concentration of serotonin (5-HT) measured in rat striatum was reduced to 75% of control 1 week after a single subcutaneous administration of dl-3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg). This decrease was prevented by pretreating the animals with ritanserin. Eighteen hours after MDMA (20 mg/kg), striatal concentrations of neurotensin-like immunoreactivity (NTLI) and of dynorphin...
The phenylisopropylamine derivative 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) has been suggested recently as a selective serotonin2 (5-HT2) receptor agonist. Because of the potential importance of such a tool for investigations of 5-HT2 receptor regulation, receptor binding studies were performed in rats after acute and chronic treatment with DOI, the selective 5-HT2 antagonist...
The interactions of the indolealkylamine N,N-dimethyltryptamine (DMT) with 5-hydroxytryptamine1A (5-HT1A) and 5-HT2 receptors in rat brain were analyzed using radioligand binding techniques and biochemical functional assays. The affinity of DMT for 5-HT1A sites labeled by [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) was decreased in the presence of 10(-4) M GTP, suggesting...
The influence of N-ethyl-3,4-methylenedioxyamphetamine (MDE) on the central serotonergic and dopaminergic systems of the rat after a single or multiple injections was studied. MDE (10 mg/kg) produced a significant decrease in the concentration of 5-hydroxytryptamine (5-HT) 1 hr later in the frontal cortex and the hippocampus without affecting the concentration of 5-hydroxyindoleacetic acid...
3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [3H]monoamines and compared to those of amphetamine and the hallucinogenic...
Following intraperitoneal administration, 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine are subject to both a very rapid uptake into, and clearance from, all tissues examined. The current studies in vivo confirm previous in vitro observations that the routes involved in the metabolism of these compounds include oxidative deamination, N-demethylation, O-demethylation, and...
The use of a series of liquid chromatographic techniques involving cation-exchange, reverse-phase and normal-phase chromatography has permitted the separation and characterisation of a number of metabolites of the psychotomimetic indolealkylamines N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine which were isolated following incubation of these compounds with rat tissue extracts. In...
Animals (rats), trained to discriminate the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant procedure, were challenged with various doses of several indolealkylamine and phenalkylamine derivatives. In both series, the alpha-methyl analogs were found to be more active than either their N-methyl or alpha-demethyl counterparts....
Abstract The skin of Bufo alvarius, a desert toad of Arizona, contains a number of indolealkylamines and their metabolites belonging to the common series of 5-hydroxyindolealkylamines and to the unusual series of 5-methoxyindolealkyIamines. The most abundant representative of 5-hydroxyindolealkylamines is, as in numerous other toads, bufotenine (up to 3 mg per g dry skin), the most abundant...