The journal of neuroscience : the official journal of the Society for Neuroscience.

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.

The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms of metabolism-mediated toxicity, drug interactions, and low bioactivation. The use of deuterium is even broader, offering the opportunity to lower the degree of epimerization, reduce the dose of coadministered boosters, and discover compounds where deuterium is the basis for the mechanism of action. Nevertheless, designing, synthesizing, and developing a successful deuterated drug is far from straightforward, and the translation from concept to practice is often unpredictable. This Perspective provides an overview of the recent developments of deuteration, with a focus on deuterated clinical candidates, and highlights both opportunities and challenges of this strategy.

Applications of Deuterium in Medicinal Chemistry

Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for treatment of neuropathic pain and the precise mechanisms underlying their effects, however, remain unclear. The inhibitory effects of these antidepressants for neuropathic pain manifest more quickly than their antidepressive effects, suggesting different modes of action. Recent studies of animal models of neuropathic pain revealed that noradrenaline is extremely important for the inhibition of neuropathic pain. First, increasing noradrenaline in the spinal cord by reuptake inhibition directly inhibits neuropathic pain through α2-adrenergic receptors. Second, increasing noradrenaline acts on the locus coeruleus and improves the function of an impaired descending noradrenergic inhibitory system. Serotonin and dopamine may reinforce the noradrenergic effects to inhibit neuropathic pain. The mechanisms of neuropathic pain inhibition by antidepressants based mainly on experimental findings from animal models of neuropathic pain are discussed in this review.

Analgesic Mechanisms of Antidepressants for Neuropathic Pain

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., menopause, mood disorders, anxiety disorders, or cognitive disorders. The first component of the pharmaceutical composition is a sedative eszopiclone. The second component of the pharmaceutical composition is trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine. The present invention also relates to a method of treating menopause, perimenopause, mood disorders, anxiety disorders, and cognitive disorders.

Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment

object located in the middle of an open field compared to saline pups. In a modified holeboard test, VPA pups spent more time exploring holes by repeated head-dipping than saline but made significantly fewer rears. VPA pups did not differ from saline pups in the elevated plus maze test but showed markedly less freezing than saline pups in a contextual fear conditioning test. Finally, VPA pups exhibited a significant lower sensitivity to pain in the hot plate test than did saline pups. In conclusion, rats exposed prenatally to VPA show a broad range of deficits consistent with autism-like symptomatology.

A.12 - divergent effects of the novel, ‘biased’, 5-ht1a receptor agonists f15599 and f13714 in a novel cognition task: object pattern separation

La presente invention concerne une forme de dosage unitaire renfermant une dose anxiolytique de zopiclone, en particulier l'eszopiclone. L'invention concerne egalement un procede permettant le traitement ou la prophylaxie de l'anxiete a l'aide d'une dose sous-sedative de zopiclone, en particulier l'eszopiclone.

Traitement de l'anxiété par l'eszopiclone

Un aspect de l'invention concerne des compositions pharmaceutiques contenant deux agents actifs ou plus qui lorsqu'on les prend ensemble peuvent etre utilises pour traiter, par exemple, la menopause, les troubles de l'humeur, l'anxiete ou les troubles cognitifs. Le premier composant de la composition pharmaceutique est un eszopiclone sedatif, le second composant de la composition pharmaceutique etant un O-desmethylvenlafaxine. L'invention concerne egalement une methode permettant de traiter la menopause, la perimenopause, les troubles de l'humeur, l'anxiete ou les troubles cognitifs.

Combinaisons d'un eszopiclone et d'un o-desmethylvenlafaxine, et methodes de traitement de la menopause et de l'humeur, de l'anxiete et des troubles cognitifs

Mark A. Varney

Papers

Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment

A.12 - divergent effects of the novel, ‘biased’, 5-ht1a receptor agonists f15599 and f13714 in a novel cognition task: object pattern separation

Traitement de l'anxiété par l'eszopiclone

Combinaisons d'un eszopiclone et d'un o-desmethylvenlafaxine, et methodes de traitement de la menopause et de l'humeur, de l'anxiete et des troubles cognitifs

Selective 5-HT1A receptor agonists biased to pERK1/2 or β-arrestin activation show differential in vivo behavioral profiles