Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Volume 18, Issue 3, 2018

Introduction: Peripheral nerve lesion is a common clinical problem that may produce longterm functional defects. Usually, crush injuries, fractures, scars, lacerations, compression, or iatrogenic reasons are reasons for nerve injuries. Unsuccessful treatment of nerve injuries causes partial or total loss of sense, motor, and autonomic functions. Despite widespread experimental studies that aimed to improve nerve healing, healing results for peripheral nerve injuries are hardly reasonable. The successes of the regenerative procedure of the nerve repair in experimental research, with topical agents, can be assessed using different methods such as morphological, electrophysiological, biochemical and functional evaluation. Although, most researchers confirm that despite good microsurgical repair and topical application of these substances, complete regeneration and functional recovery of the injured nerves are almost never achieved. Conclusion: This study aimed to make a comparison between topical pharmacological agents at the peripheral nerve lesion and methods used for evaluating the success of the repair process. For this purpose, we reviewed studies conducted on some of the most commonly used pharmacological agents as well as their properties in the repair of peripheral nerve lesions.

Background: Recorded history shows that malaria has plagued mankind for centuries, if not millennia, with the disease infecting and affecting several body tissues, organs and systems; including the central nervous system. Cerebral malaria is a severe form of malaria that may be associated with acute and chronic general behavioural, neurological or neuropsychiatric manifestations. The observation that the use of certain antimalaria drugs may also be associated with behavioural, neurochemical and structural brain changes complicates the picture, as both the infection and its treatment may cause significant changes in brain structure/function and behaviour. However, scientific literature appears to have made only a limited (if any) attempt at distinguishing the central nervous system effects of malaria infection from those of antimalaria drugs, and those that may occur due to possible interactions between the parasite and the drugs; as it relates to behaviour, brain neurochemistry, and neuromorphology. In this narrative review, we examine available literature dealing with the subject of the central effects of: The plasmodium parasite, antimalaria drugs, and interactions between drugs and the parasite; with a view to delineating the behavioural, neurochemical and neuromorphological changes that may occur due the infection, the drugs, and with the interactions of the drugs with the parasites inside the host. Conclusion: While research examining this subject matter continues to advance our understanding of the interactions amongst parasite/drug and the brain; for now, there are more questions than answers in relation to the effects of antimalaria drug/parasite interactions on the brain.

Introduction: The brain is the most complicated organ in a vertebrate's organism. In a human, it contains about two hundred billions of neurons and non-neuronal cells. To understand the mechanisms of the brain functions is the great challenge for the researchers. Much is already done on this way; however, it remains a lot to do still, and to get deeper knowledge, new approaches should be developed. One of this is to use benefits that nanotechnology brings in this area. Nanotechnology opens up unique opportunities, not only for material science research, but also for biology, medicine, and many other disciplines. There are several kinds of nanoparticles that can be applied in brain studies, Quantum Dots (QD) being so far most often used. QD are semiconductor light emitting nanocrystals with nanometer-sized structures of unique optical properties. They have bright fluorescence, are resistant to bleaching and able of emitting fluorescent light of different wavelengths. These properties make QD perfect tools for visualization of brain structures and mechanisms underlying its functions. Due to unique QD properties, even single molecules under study can be observed. Moreover QDs can be used for brain-targeted drug delivery. Conclusion: In this review, the application of quantum dots for the brain research is considered and benefits that it can bring are discussed.

Introduction: Suicide is still a major event of human mortality worldwide. Yet human suicide prediction, prevention and therapeutic systems at this moment are generally ineffective in the clinic. No diagnostic system is reliable for significantly suicidal prevention and mortality reduction. As a result, human suicide etiopathologic investigation (especially at genetic/molecular levels in the clinical settings) is quite necessary. In order to boost human suicide researches, emerging human suicide diagnostic/treatment study will be transformed from clinical symptom observations into new generations of candidate drug targets and therapeutics. To achieve this goal, associations between suicidal etiopathologic identification, genetic/bioinformatics-based diagnostics and putative drug targets must be exploited than ever before. After all, the interaction and relationships between environmental/ genetic/molecular clues and overall patient's risk prediction (environmental influences and different therapeutic targets/types) should be found out. Conclusion: In the future, effective clinical suicide prediction, prevention and therapeutic systems can be established via scientific expeditions and causality discovery.

Introduction: One promising target for novel psychotropic drugs is the 5-HT6 receptor, GProtein- Coupled Receptor (GPCR) family, displaying seven transmembrane domains. There is considerable interest in how both 5-HT6 receptor agonist and antagonist compounds can have marked procognitive effects. Methods: An exact structure of the 5-HT6 receptor is not available, so application of powerful methods of (Q)SAR and molecular modelling, which play an essential role in modern drug design, are currently limited to structure-based homology models. The present study is devoted to a detailed QSAR analysis of 61 drugs (26 agonists and 35 antagonists) acting on the 5-HT6 receptor (rattus norvegicus and homo sapiens). Five classification methods were used: k-Nearest Neighbors (k-NN), Logistic Regression (LG), Linear Discriminant Analysis (LDA), Random Forest (RF), and Support Vector Machine (SVM). Multiple Regression Analysis (MRA) was involved also for regression analysis. Spectra of Inter Atomic Interactions (SIAI) were applied in the search for ligand centres interacting with the 5- HT6 receptor. Results & Conclusion: SAR and QSAR models based on the use of HYBOT, MOLTRA, VolSurf+, and SYBYL programs, and having cross-validated coefficients of determination of at least 0.80, show a predominant influence of H-bond acceptor ability and hydrophobicity on the type of ligand activity and degree of inhibition.

Background: Gamma-Decanolactone (GD) is a monoterpene compound that presents anticonvulsant effect in acute and chronic models of epilepsy and it acts as a noncompetitive glutamate antagonist. Objective: This study evaluated the anticonvulsant profile and the possible mechanism of action of GD in seizures induced by isoniazid (INH; 250 mg/kg), picrotoxin (PCT; 5 mg/kg) and 4- aminopyridine (4-AP; 13 mg/kg) in male mice. Method: Thirty minutes before the convulsants administration, animals received a single administration of saline, GD (100 or 300 mg/kg) or the positive control diazepam (DZP; 2 mg/kg). The parameters evaluated were the latency to the first seizure and the occurrence of clonic forelimb seizures. The rotarod performance test was used to evaluate the neurotoxicity of GD (300 mg/kg). Also, the DZPinduced sleep test was used. Results: DZP increased the latency to the first seizure on all used models and decreased the percentage of seizures in two of the three behavioral models. GD was able to prolong the latency to the first seizure and decreased the percentage of seizures induced by INH and 4-AP, but not by PCT. It reduced the latency to fall off the rotarod test only at the time of 30 min. In the DZP-induced sleep test, GD shortened the onset and prolonged the time of sleep. Conclusion: Our findings suggested that GD reduced the convulsive behavior in the seizure models used here and it could modulate GABA pathways and affect potassium channels directly or indirectly, involving more than one cellular target in the central nervous system.