PROMISING DIRECTIONS FOR THE APPLICATION OF PIPERIDINE DERIVATIVES AS STRUCTURAL COMPONENTS OF NEUROTROPIC DRUGS

Piperidine is one of the most common heterocycles, and its derivatives are found in many pharmacological groups, including neurotropic drugs. These compounds are numerous among analgesics, and, in addition to “classical” promedol, fentanyl and its derivatives, the paper presents the results of studying new compounds with analgesic activity and piperidine cycle. Reviews of such piperidine antipsychotics as haloperidol and risperidone have been considered, and new compounds showing antipsychotic activity through their effects on dopamine and serotonin receptors have been elucidated. The data on the influence of methylphenidate on the brain in case of attention deficit/ hyperactivity disorder (ADHD) have been analyzed, which help to understand the disturbances occurring in this disease. Tiagabine has been considered as an antiepileptic agent reducing the number of seizures in resistant forms of partial epilepsy, as well as the activation of microglia and may be effective in neurodegenerative diseases. The last section is devoted to drugs for the treatment of Alzheimer’s disease (AD), namely donepezil, its modifications, and some new compounds potentially capable of inhibiting AD progression through the inhibition of Aβ42 protein synthesis.

Download Full-text

Family-based Association Study Between the Brain Derived Neurotrophic Factor (BDNF) Gene and the Attention Deficit Hyperactivity Disorder in a Mexican Population

10.26226/morressier.58a41cf6d462b8028d892521 ◽

2017 ◽

Author(s):

Juan Pablo Sánchez de la Cruz

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Association Study ◽

Attention Deficit ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Mexican Population ◽

Bdnf Gene ◽

Hyperactivity Disorder ◽

Family Based ◽

The Brain

Download Full-text

A Computational Perspective on Drug Discovery and Signal Transduction Mechanism of Dopamine and Serotonin Receptors in the Treatment of Schizophrenia

Current Pharmaceutical Biotechnology ◽

10.2174/1389201015666140909150033 ◽

2014 ◽

Vol 15 (10) ◽

pp. 916-926 ◽

Cited By ~ 2

Author(s):

Peng Lian ◽

Lili Xu ◽

Chuanrong Geng ◽

Yuanyuan Qian ◽

Wei Li ◽

...

Keyword(s):

Signal Transduction ◽

Drug Discovery ◽

Serotonin Receptors ◽

Transduction Mechanism ◽

Signal Transduction Mechanism ◽

Computational Perspective ◽

Dopamine And Serotonin Receptors

Download Full-text

Substituted N,N-Dimethyl-3-(phenylthio)- and -4-(phenylthio)benzylamines

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19920194 ◽

1992 ◽

Vol 57 (1) ◽

pp. 194-203 ◽

Cited By ~ 5

Author(s):

Karel Šindelář ◽

Vojtěch Kmoníček ◽

Marta Hrubantová ◽

Zdeněk Polívka

Keyword(s):

Serotonin Receptors ◽

Hydrobromic Acid ◽

Antidepressant Activity ◽

Benzoic Acids ◽

Lithium Aluminium Hydride ◽

Acid Chlorides ◽

Activity Inhibition ◽

Lithium Aluminium ◽

The Brain

(Arylthio)benzoic acids IIa - IIe and VIb - VId were transformed via the acid chlorides to the N,N-dimethylamides which were reduced either with diborane "in situ" or with lithium aluminium hydride to N,N-dimethyl-(arylthio)benzylamines Ia - Ie and Vb - Vd. Leuckart reaction of the aldehydes IX and X with dimethylformamide and formic acid afforded directly the amines Va and Ve. Demethylation of the methoxy compounds Ia and Ve with hydrobromic acid resulted in the phenolic amines If and Vf. The most interesting N,N-dimethyl-4-(phenylthio)benzylamine (Va) hydrochloride showed affinity to cholinergic and 5-HT2 serotonin receptors in the rat brain and some properties considered indicative of antidepressant activity (inhibition of serotonin re-uptake in the brain and potentiation of yohimbine toxicity in mice).

Download Full-text

SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

Translational Psychiatry ◽

10.1038/s41398-021-01344-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Camille Dupuy ◽

Pierre Castelnau ◽

Sylvie Mavel ◽

Antoine Lefevre ◽

Lydie Nadal-Desbarats ◽

...

Keyword(s):

Oxidative Stress ◽

Attention Deficit Hyperactivity Disorder ◽

Animal Model ◽

Metabolic Pathways ◽

Neurodevelopmental Disorder ◽

Hyperactivity Disorder ◽

Pathophysiological Condition ◽

The Brain ◽

And Oxidative Stress ◽

Peripheral Samples

AbstractAttention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.

Download Full-text