Current medicinal chemistry
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Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. ⋯ These significant findings on HCQ suggest the potential therapeutic applications of HCQ for treatment of many diseases, such as cancers, skin disease, antiphospholipid syndrome, etc. This review focuses on recent in vitro and clinical trials on its pharmacological mechanisms, therapeutic activities, and potential adverse effects.
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Balance between excitatory glutamate and inhibitory GABA neurotransmitter is essential and critical for proper development and functioning of brain. GABAergic (gamma aminobutyric acid) and glutamatergic interneurons maintain excitability, integrity and synaptic plasticity. Several evidences implicated relative loss of inhibitory GABA with corresponding glutamate mediated hyper-excitation in development of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). ⋯ Several studies demonstrated the imbalance of excitatory/inhibitory neurotransmitters resulting from neurodevelopmental impairments in glutamatergic and GABAergic system, which might resemblesa common pathological mechanism for the developmental disorders. This review focuses on the necessity for developing GABA enhancing and glutamate suppressing drug candidates and illustrates the role of GABAergic and glutamatergic system in cognition and memory impairment involved in neurodevelopmental disorders with emphasis on ASD and ADHD. The review also highlights the newly emerging drugs for neurodevelopmental disorders.
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Recent evidence suggests that the development of Alzheimer's disease (AD) and related cognitive loss is due to mutations in the Amyloid Precursor Protein (APP) gene on chromosome 21 and increased activation of eukaryotic translation initiation factor-2α (eIF2α) phosphorylation. The high level of misfolded and unfolded proteins loading in Endoplasmic Reticulum (ER) lumen triggers ER stress and as a result Unfolded Protein Response (UPR) pathways are activated. Stress-dependent activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the significant elevation of phospho-eIF2α. ⋯ Thus, blocking PERK-dependent eIF2α phosphorylation through specific, small-molecule PERK branch inhibitors seems to be a potential treatment strategy for AD individuals. That may contribute to the restoration of global translation rates and reduction of expression of ATF4 and BACE1. Hence, the treatment strategy can block accelerated β -amyloidogenesis by reduction in APP cleaving via the BACE1-dependent amyloidogenic pathway.
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Alcoholism is an increasing problem all over the world, and nowadays especially amongst teenagers. Although several drug treatments have been proposed for this condition, only a few have demonstrated a significant efficacy. ⋯ This drug can be very helpful in reducing the alcohol intake, and, as such, it can be considered one of the first and fundamental steps towards alcohol abstinence. The aim of this review is to discuss and comment on the available literature on nalmefene, as well as on novel treatment strategies of this condition (and perhaps of other addictions) opened by this latest pharmacological approach.
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The use of the cannabis plant for various medical indications by cancer patients has been rising significantly in the past few years in several European countries, the US and Israel. The increase in use comes from public demand for the most part, and not due to a scientific basis. Cannabis chemistry is complex, and the isolation and extraction of the active ingredient remain difficult. ⋯ The clinical evidence of the efficacy of cannabis for these indications is only partial. However, recent scientific data from studies with THC and cannabidiol combinations report the first clinical indication of cancer-related pain relief. The difficulties of performing research into products that are not medicinal, such as cannabis, have not allowed a true study of the cannabis plant extract although, from the public point of view, such studies are greatly desirable.