Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.

Pharmacomodulation of membrane channels is an essential topic in the study of physiological conditions and disease status. Transient receptor potential (TRP) channels are one such family of nonselective cation channels that have an important influence. In mammals, TRP channels consist of seven subfamilies with a total of twenty-eight members. Evidence shows that TRP channels mediate cation transduction in neuronal signaling, but the full implication and potential therapeutic applications of this are not entirely clear. In this review, we aim to highlight several TRP channels which have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy. Recent findings suggest that TRPM (melastatin), TRPV (vanilloid), and TRPC (canonical) are of particular relevance to these phenomena. The research reviewed in this paper validates these TRP channels as potential targets of future clinical treatment and offers patients hope for more effective care.

Suboxone: History, controversy, and open questions.

There are more than 200 opioid overdose deaths each day in the US. In combating this epidemic we look to available treatment tools. Here, we find only three medications approved by the Food and Drug Administration (FDA) for the treatment of opioid use disorder. Of the three, buprenorphine is of particular importance due to its reduced overdose potential as a partial opioid agonist. Evidence supports its clinical equivalence to its full agonist cousin methadone, and suggests that it is better slated for long-term treatment of opioid use disorder compared to the non-selective opioid antagonist naltrexone. Buprenorphine is most popularized within Suboxone, a medication which also contains the non-selective opioid antagonist naloxone. The naloxone has no additional effect when the drug is taken as instructed, as it is intended to prevent diversion in those that would attempt to inject the medication. While Suboxone is regarded by some as the future of medical treatment, others have expressed concerns. This review aims to explore the history, controversy, and open questions that surround buprenorphine and its most prescribed variation, Suboxone. These include its pharmacological, legislative, and social history, alternative indications, efficacy as a treatment of opioid use disorder, and more. Armed with this information, the reader will have a more in-depth and holistic understanding of the medication's place in their community.

Amylin and Secretases in the Pathology and Treatment of Alzheimer's Disease.

Alzheimer's disease remains a prevailing neurodegenerative condition which has an array physical, emotional, and financial consequences to patients and society. In the past decade, there has been a greater degree of investigation on therapeutic small peptides. This group of biomolecules have a profile of fundamentally sound characteristics which make them an intriguing area for drug development. Among these biomolecules, there are four modulatory mechanisms of interest in this review: alpha-, beta-, gamma-secretases, and amylin. These protease-based biomolecules all have a contributory role in the amyloid cascade hypothesis. Moreover, the involvement of various biochemical pathways intertwines these peptides to have shared regulators (i.e., retinoids). Further clinical and translational investigation must occur to gain a greater understanding of its potential application in patient care. The aim of this narrative review is to evaluate the contemporary literature on these protease biomolecule modulators and determine its utility in the treatment of Alzheimer's disease.

Acid-Sensing Ion Channel 2: Function and Modulation.

Acid-sensing ion channels (ASICs) have an important influence on human physiology and pathology. They are members of the degenerin/epithelial sodium channel family. Four genes encode at least six subunits, which combine to form a variety of homotrimers and heterotrimers. Of these, ASIC1a homotrimers and ASIC1a/2 heterotrimers are most widely expressed in the central nervous system (CNS). Investigations into the function of ASIC1a in the CNS have revealed a wealth of information, culminating in multiple contemporary reviews. The lesser-studied ASIC2 subunits are in need of examination. This review will focus on ASIC2 in health and disease, with discussions of its role in modulating ASIC function, synaptic targeting, cardiovascular responses, and pharmacology, while exploring evidence of its influence in pathologies such as ischemic brain injury, multiple sclerosis, epilepsy, migraines, drug addiction, etc. This information substantiates the ASIC2 protein as a potential therapeutic target for various neurological, psychological, and cerebrovascular diseases.

Striatonigrostriatal Spirals in Addiction.

A biological reward system is integral to all animal life and humans are no exception. For millennia individuals have investigated this system and its influences on human behavior. In the modern day, with the US facing an ongoing epidemic of substance use without an effective treatment, these investigations are of paramount importance. It is well known that basal ganglia contribute to rewards and are involved in learning, approach behavior, economic choices, and positive emotions. This review aims to elucidate the physiological role of striatonigrostriatal (SNS) spirals, as part of basal ganglia circuits, in this reward system and their pathophysiological role in perpetuating addiction. Additionally, the main functions of neurotransmitters such as dopamine and glutamate and their receptors in SNS circuits will be summarized. With this information, the claim that SNS spirals are crucial intermediaries in the shift from goal-directed behavior to habitual behavior will be supported, making this circuit a viable target for potential therapeutic intervention in those with substance use disorders.