Wiktor Petrov

Background: Dexmedetomidine is a highly selective α₂-adrenergic receptor agonist increasingly used in neonatal and pediatric intensive care and anesthesia. Its central mechanism of action and experimental evidence suggesting anti-inflammatory, anti-apoptotic, antioxidant, and antiexcitotoxic effects have raised interest in its influence on the developing central nervous system. At the same time, uncertainty remains regarding its long-term neurodevelopmental consequences and the clinical relevance of reported neurological safety signals. Objective: This review aimed to critically evaluate the neurological and neurodevelopmental effects of dexmedetomidine in neonatal and pediatric populations, with particular emphasis on potential neuroprotective effects, acute neurological safety signals, and long-term neurodevelopmental outcomes. Methods: A structured literature review of publications from 1989 to 2026 was conducted. Evidence included primary clinical studies, prospective and retrospective cohorts, randomized controlled trials, follow-up studies, case reports, and secondary evidence syntheses, including systematic reviews and meta-analyses. Long-term neurodevelopmental and cognitive outcomes were analyzed separately from acute neurological effects and neurological safety signals. Secondary evidence was evaluated independently from primary studies to avoid double counting of participants. Preclinical and surrogate evidence of neuroprotection was distinguished from direct evidence of long-term human neurodevelopmental benefit. Results: Dexmedetomidine was associated with measurable effects on the developing central nervous system, although their clinical significance varied across populations and study designs. In neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia, secondary evidence suggested a lower pooled seizure risk with dexmedetomidine compared with conventional sedatives, although substantial heterogeneity and observational study designs limited causal interpretation. In pediatric anesthesia, dexmedetomidine reduced sevoflurane-related emergence agitation, but this short-term behavioral endpoint does not constitute evidence of long-term neuroprotection. Preclinical studies demonstrated attenuation of sevoflurane-associated neuronal migration delay, restoration of dendritic spine density, and improvement of transient somatosensory dysfunction, supporting a potential synaptic and developmental neuroprotective effect. However, clinical studies did not consistently demonstrate improvements in cognition, behavior, or long-term neurodevelopment. Reported neurological safety signals included altered cerebral activity, seizure-related events, abnormal movements, and posterior reversible encephalopathy syndrome following abrupt dexmedetomidine withdrawal with rebound hypertension. Conclusions: Dexmedetomidine exerts measurable effects on the developing central nervous system, but current evidence is insufficient to classify it as either a clinically proven neuroprotective agent or as directly neurotoxic to the developing human brain. Available data support short-term neurological effects and preclinical neuroprotective potential, whereas long-term human neurodevelopmental consequences remain uncertain. Further prospective studies using validated longitudinal neurodevelopmental outcomes are required to determine its long-term neurological safety and potential neuroprotective benefit. Anesthetic agents and method of discontinuation. Further prospective, adequately powered studies with standardized dosing and long-term neurodevelopmental follow-up are required.

The term ‘dementia’ encompasses a diverse group of progressive neurodegenerative disorders, the common feature of which is the deterioration of higher cortical functions. This process not only involves memory deficits and language communication disorders, but also executive dysfunction and loss of emotional control, which ultimately leads to a complete loss of the patient’s independence. Within this group of disorders, Alzheimer’s disease (AD) presents the most serious clinical challenge, characterized by a unique neuropathological triad: the presence of extracellular β-amyloid plaques, intracellular neurofibrillary tangles of tau protein, and widespread dysfunction of cholinergic transmission. The cholinergic hypothesis remains the cornerstone of the current understanding of cognitive impairment in AD. It posits that progressive dementia is caused by the selective degeneration of neurons in the anterior basal forebrain, resulting in a drastic reduction in acetylcholine (ACh) levels in the synaptic cleft. In the absence of a causal treatment, acetylcholinesterase inhibitors (AChEIs) remain the standard of care. Their pharmacological action is based on the inhibition of the AChE enzyme, which allows neurotransmission deficits to be compensated for by prolonging the half-life of acetylcholine at the synapse. This literature review presents a synthesis of the efficacy and safety of classic and novel AChEIs. A comprehensive search of the PubMed, Scopus, and Cochrane Library databases was conducted for clinical data published up to 2026. Evidence from key trials indicates that standard AChEIs induce significant cognitive stabilization compared to placebo, with rivastigmine maximizing daily living parameters via transdermal delivery. However, their therapeutic impact remains strictly symptomatic without arresting neurodegeneration. Conversely, emerging agents like huperzine A and the translation-blocker Posiphen demonstrate disease-modifying potential by modulating CSF biomarkers associated with amyloid and tau proteins. Clinically, while traditional regimens are limited by gastrointestinal toxicities, transitioning toward innovative multi-target structures represents a necessary shift to address both cognitive decline and neurodegeneration.

Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines.

Insomnia is a common and complex disorder, rooted in the dysregulation of circadian rhythms, impaired neurotransmitter function, and disturbances in sleep–wake homeostasis. While conventional hypnotics such as benzodiazepines and Z-drugs are effective in the short term, their use is limited by a high potential for dependence, cognitive side effects, and withdrawal symptoms. In contrast, melatonergic receptor agonists—melatonin, ramelteon, tasimelteon, and agomelatine—represent a pharmacologically targeted alternative that modulates MT1 and MT2 receptors, which are pivotal to the regulation of circadian timing and sleep initiation. Clinical evidence supports the efficacy of these agents in reducing sleep onset latency, extending total sleep duration, and re-aligning disrupted circadian rhythms, particularly among older individuals and patients with non-24 h sleep–wake disorders. Notably, agomelatine offers additional antidepressant properties through selective antagonism of the 5-HT_2C receptor in micromolar concentrations. In contrast, its agonistic activity at melatonergic receptors is observed in the low sub-nanomolar range, which illustrates the complexity of this drug’s interactions with the human body. All compounds reviewed demonstrate a generally favorable safety and tolerability profile. Accumulating evidence highlights that selected medicinal plants, such as chamomilla, lemon balm, black cumin, valeriana, passionflower and lavender, may exert relevant hypnotic or anxiolytic effects, thus complementing melatonergic strategies in the management of insomnia. This structured narrative review presents a comprehensive analysis of the molecular pharmacology, receptor affinity, signaling pathways, and clinical outcomes associated with melatonergic agents. It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep–wake disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder generally associated with pediatric patients and in lesser extent with adults. Patients diagnosed with ADHD have a higher likelihood of developing addiction. Consequently, a disorder that frequently co-occurs with ADHD is Substance Use Disorder (SUD). The pharmaceuticals prescribed in the treatment of ADHD are predominantly stimulants, such as methylphenidate and amphetamines, which possess a high addiction potential. The objective of this study is to examine the risk of developing substance dependence during stimulant treatment in individuals with ADHD who have a natural predisposition to addiction, with particular emphasis on adult patients with a history of SUD. Our literature review was conducted using research papers from PubMed, Google Scholar, Embase, ProQuest and ScienceDirect. The main results from our review are as follows: (i) the majority of studies indicate that the administration of stimulants in the treatment of ADHD does not increase the risk of developing Substance Use Disorder; (ii) stimulants may also be used in the treatment of SUD; (iii) while pharmacotherapy is a crucial part of ADHD treatment, a holistic approach comprising pharmacological and non-pharmacological therapy is most effective; (iv) holistic management of ADHD is necessary to improve patients’ quality of life to the greatest extent possible.

The orexin (hypocretin) system plays a central role in regulating the sleep–wake cycle through two neuropeptides, orexin-A and orexin-B, which act on OX1R and OX2R receptors. Emerging evidence links heightened orexin signaling with the pathophysiology of chronic insomnia. This review outlines the neurobiology of the orexinergic system, compares the pharmacological profile of dual orexin receptor antagonists (DORAs) to traditional GABAergic hypnotics, and evaluates the clinical efficacy and safety of Suvorexant, Lemborexant, and Daridorexant. DORAs function by selectively dampening orexin-driven arousal, thereby facilitating sleep onset and maintenance without disrupting natural sleep architecture. Clinical trials have shown that these agents significantly reduce sleep latency and enhance sleep continuity, with a favorable side effect profile. Overall, DORAs represent a distinct and clinically advantageous option for insomnia treatment, with growing interest in their potential utility across mood, anxiety, and neurodegenerative disorders.