Acceleration and inhibition of tryptophan metabolism.

Tryptophan is functionally important in biological systems, as the free amine acid, as a component of proteins, and as a precursor of physiologically active substances. If administered in excess amounts, it modifies carbohydrate and fat metabolism and the activities of some enzymes. A dietary deficiency of this essential amino acid results in attenuated growth, and alterations in the metabolism of certain substances. Within the protein molecule, tryptophan is believed to play a role as an intermediate in some enzymic reactions. [...

Endocannabinoid system and exogenous cannabinoids in depression and anxiety: a review.

There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Although the common belief that cannabinoids, including cannabis, its main studied components-tetrahydrocannabinol (THC) and cannabidiol (CBD)-or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement

Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior.

ABSTRACT The self-administration of cocaine was compared with that of bupropion

-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) Analogues: A Promising Class of Monoamine Uptake Inhibitors

Dopamine, serotonin, and norepinephrine are essential for neurotransmission in the mammalian system. These three neurotransmitters have been the focus of considerable research because the modulation of their production and their interaction at monoamine receptors has profound effects upon a multitude of pharmacological outcomes. Our interest has focused on neurotransmitter reuptake mechanisms in a search for medications for cocaine abuse. Herein we describe the synthesis and biological evaluation of an array of 2-aminopentanophenones. This array has yielded selective inhibitors of the dopamine and norepinephrine transporters with little effect upon serotonin trafficking. A subset of compounds had no significant affinity at 5HT 1A , 5HT 1B , 5HT 1C , D 1 , D 2 , or D 3 receptors. The lead compound, racemic 1-(4-methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one 4a, was resolved into its enantiomers and the S isomer was found to be the most biologically active enantiomer. Among the most potent of these DAT/NET selective compounds are the 1-(3,4-dichlorophenyl)-(4u) and the 1-naphthyl-(4t) 2-pyrrolidin-1-yl-pentan-1-one analogues