GABAA receptors: structure, function, pharmacology, and related disorders

Journal of Genetic Engineering and Biotechnology, Journal Year: 2021, Volume and Issue: 19(1), P. 123 - 123

Published: Aug. 21, 2021

γ-Aminobutyric acid sub-type A receptors (GABAARs) are the most prominent inhibitory neurotransmitter in CNS. They a family of ligand-gated ion channel with significant physiological and therapeutic implications.GABAARs heteropentamers formed from selection 19 subunits: six α (alpha1-6), three β (beta1-3), γ (gamma1-3), ρ (rho1-3), one each δ (delta), ε (epsilon), π (pi), θ (theta) which result production considerable number receptor isoforms. Each isoform exhibits distinct pharmacological properties. However, majority GABAARs composed two subunits, subunit arranged as γ2β2α1β2α1 counterclockwise around center. The mature has central chloride gated by GABA modulated variety different drugs. Changes synthesis or release may have effect on normal brain function. Furthermore, molecular interactions effects caused drugs extremely complex. This is due to structural heterogeneity receptors, existence multiple allosteric binding sites well wide range ligands that can bind them. Notably, dysfunction GABAergic system contributes development several diseases. Therefore, understanding relationship between GABAA deficits CNS disorders thus impact discovery disease pathogenesis drug development.To date, few reviews discussed detail. Accordingly, this review aims summarize current structural, physiological, properties GABAARs, shedding light common associated disorders.

Language: Английский

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G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 3, 2023

Neuropsychiatric disorders are multifactorial with diverse aetiological factors. Identifying treatment targets is challenging because the diseases resulting from heterogeneous biological, genetic, and environmental Nevertheless, increasing understanding of G protein-coupled receptor (GPCR) opens a new possibility in drug discovery. Harnessing our knowledge molecular mechanisms structural information GPCRs will be advantageous for developing effective drugs. This review provides an overview role various neurodegenerative psychiatric diseases. Besides, we highlight emerging opportunities novel GPCR address recent progress development.

Language: Английский

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Molecular and Cellular Mechanisms of Action of Cannabidiol

Molecules, Journal Year: 2023, Volume and Issue: 28(16), P. 5980 - 5980

Published: Aug. 9, 2023

Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa, a plant used for centuries both recreational and medicinal purposes. CBD lacks psychotropic effects of Δ9-tetrahydrocannabinol (Δ9-THC) has shown great therapeutic potential. exerts wide spectrum at molecular, cellular, organ level, affecting inflammation, oxidative damage, cell survival, pain, vasodilation, excitability, among others, modifying many physiological pathophysiological processes. There evidence that may be effective in treating several human disorders, like anxiety, chronic psychiatric pathologies, cardiovascular diseases, even cancer. Multiple cellular pre-clinical studies using animal models disease trials have an overall safe profile. In this review article, we summarize pharmacokinetics data, putative mechanisms action CBD, reported to give comprehensive list findings major attributed compound.

Language: Английский

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Cardiotoxic effects of common and emerging drugs: role of cannabinoid receptors

Clinical Science, Journal Year: 2024, Volume and Issue: 138(6), P. 413 - 434

Published: March 1, 2024

Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in regulation heart disease, with mounting evidence linking CBRs pathogenesis progression drug-induced cardiotoxicity. This review aims summarize fundamental characteristics two well-documented (CB1R CB2R) from aspects molecular structure, signaling functions cardiovascular physiology pathophysiology. Moreover, we describe CB1R CB2R occurrence induced by drugs such as antipsychotics, anti-cancer drugs, marijuana, some emerging synthetic cannabinoids. We highlight 'yin-yang' relationship between propose future perspectives CBR-based translational medicine toward curation clinical monitoring.

Language: Английский

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Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses

Toxins, Journal Year: 2021, Volume and Issue: 13(2), P. 117 - 117

Published: Feb. 5, 2021

For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational spiritual purposes. Phytocannabinoids are family compounds that found in the cannabis plant, which is known its psychotogenic euphoric effects; main psychotropic constituent Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects cannabinoids result interactions between those cannabinoid receptors, CB1 CB2, located many parts human body. used therapeutic agent treating pain emesis. Some clinically applied chronic pain, particularly cancer multiple sclerosis-associated appetite stimulation anti-emesis HIV/AIDS patients, spasticity treatment sclerosis epilepsy patients. Medical varies from chemical content THC cannabidiol (CBD), modes administration, safety. Despite cannabis, exposure to high concentrations THC, compound responsible most intoxicating experienced by users, could lead psychological events adverse affect almost all body systems, such neurological (dizziness, drowsiness, seizures, coma, others), ophthalmological (mydriasis conjunctival hyperemia), cardiovascular (tachycardia arterial hypertension), gastrointestinal (nausea, vomiting, thirst), mainly associated with use. toxicity children more concerning can cause serious acute symptoms (stupor), lethargy, even coma. More countries legalizing commercial production sale medicinal use, some use well. Liberalization laws led increased incidence toxicity, hyperemesis syndrome, lung disease disease, reduced fertility, tolerance, dependence prolonged This review focuses on potential cannabinoids, well toxic various systems.

Language: Английский

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Molecular Mechanism of Cannabinoids in Cancer Progression

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3680 - 3680

Published: April 1, 2021

Cannabinoids are a family of heterogeneous compounds that mostly interact with receptors eliciting several physiological effects both in the central and peripheral nervous systems organs. They exert anticancer action by modulating signaling pathways involved cancer progression; furthermore, induced their use depend on type tumor components endocannabinoid system. This review will explore mechanism cannabinoids proliferation, neovascularisation, migration, invasion, metastasis, angiogenesis.

Language: Английский

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A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of β-caryophyllene, a dietary cannabinoid

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 140, P. 111639 - 111639

Published: June 3, 2021

The endocannabinoid system (ECS), a conserved physiological emerged as novel pharmacological target for its significant role and potential therapeutic benefits ranging from neurological diseases to cancer. Among both, CB1 CB2R types, have received attention effects antioxidant, anti-inflammatory, immunomodulatory antiapoptotic that can be achieved without causing psychotropic adverse through CB1R. ligands activate are of endogenous, synthetic plant origin. In recent years, β-caryophyllene (BCP), natural bicyclic sesquiterpene in cannabis well non-cannabis plants, has due selective agonist property on CB2R. BCP been studied variety pathological conditions mediating property. focus the present manuscript is represent mediated mechanisms BCP. narrative review summarizes insights into CB2R-selective properties such cardioprotective, hepatoprotective, neuroprotective, nephroprotective, gastroprotective, chemopreventive, immunomodulator. available evidences suggest BCP, an important candidate origin endowed with may provide rationale pharmacotherapeutic application pharmaceutical development like drug. Additionally, given wide availability edible plants dietary use, safety, no toxicity, promoted nutraceutical functional food general health well-being. Further, studies needed explore opportunities preventive applications use human diseases.

Language: Английский

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Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Neuropsychopharmacology, Journal Year: 2022, Volume and Issue: 47(7), P. 1315 - 1330

Published: April 22, 2022

Abstract Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where outcome was analgesia or dose requirements. We searched Scopus, Cochrane Central Registry Controlled Trials, Medline, Embase (2016 onwards). Ninety-two met search criteria including 15 ongoing trials. Meta-analysis seven found median effective (ED 50 ) morphine administered with delta-9-tetrahydrocannabinol 3.5 times lower (95% CI 2.04, 6.03) than ED alone. Six no evidence increased abuse liability cannabinoid administration. Of five healthy-volunteer experimental pain studies, two pain, decreased one bothersomeness administration; three demonstrated that increase liability. Three randomized controlled trials (RCTs) in acute pain. four RCTs patients cancer effect administration (mean difference −3.8 mg, 95% −10.97, 3.37) percentage change scores 1.84, −2.05, 5.72); more adverse events compared placebo (risk ratio 1.13, 1.03, 1.24). chronic non-cancer trials; low-quality study control arm, single-dose reported cannabinoids. treatment dronabinol. Meta-analyses observational 39% cessation 0.15, 0.64, I 2 95.5%, eight studies), 85% reduction 0.99, 92.8%, studies). In summary, demonstrate potential context analgesia, contrast to higher-quality did not provide effects.

Language: Английский

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The Transdermal Delivery of Therapeutic Cannabinoids

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(2), P. 438 - 438

Published: Feb. 18, 2022

Recently, several studies have indicated an increased interest in the scientific community regarding application of Cannabis sativa plants, and their extracts, for medicinal purposes. This plant enormous potential has been legalised increasing number countries globally. Due to recent changes therapeutic recreational legislation, cannabis cannabinoids are now frequently permitted use clinical settings. However, with highly lipophilic features very low aqueous solubility, prone degradation, specifically solution, as they light-, temperature-, auto-oxidation-sensitive. Thus, plant-derived developed oral, nasal-inhalation, intranasal, mucosal (sublingual buccal), transcutaneous (transdermal), local (topical), parenteral deliveries. Among these administrations routes, topical transdermal products usually a higher bioavailability rate prolonged steady-state plasma concentration. Additionally, eliminate psychotropic impacts drug by its diffusion into nonreactive, dead stratum corneum. modality avoids oral administration and, thus, first-pass metabolism, leading constant cannabinoid levels. review article investigates practicality delivering via skin accordance existing literature.

Language: Английский

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Endocannabinoid System: Chemical Characteristics and Biological Activity

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 148 - 148

Published: Jan. 19, 2023

The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and associated enzymatic apparatus responsible for maintaining energy homeostasis cognitive processes. Several physiological effects cannabinoids are exerted through interactions with various such as CB1 CB2 vanilloid recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, GPR19). Anandamide (AEA) 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding both receptors. plays a critical role chronic pain mood disorders extensively because its wide therapeutic potential it is promising target development new drugs. Phytocannabinoids synthetic have shown varied affinities relevant treatment several neurological diseases. This review provides description components discusses how phytocannabinoids other exogenous compounds may regulate balance. Furthermore, we show hypo- or hyperfunctionality body related disorders, even integrative complementary health practices (ICHP) harmonizing eCB.

Language: Английский

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