Displaying publications 21 - 40 of 80 in total

Abstract:
Sort:
  1. Kratom and Future Treatment for the Opioid Addiction and Chronic Pain: Periculo Beneficium?
    Ismail I, Wahab S, Sidi H, Das S, Lin LJ, Razali R
    Curr Drug Targets, 2019;20(2):166-172.
    PMID: 28443503 DOI: 10.2174/1389450118666170425154120
    Kratom (Mitragyna speciosa), a naturally existing plant found in South-East Asia, is traditionally used as a herb to help elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (µ) and kappa (κ). The role of neural reward pathways linked to µ-opioid receptors and both dopaminergic and gamma-Aminobutyric acid (GABA)-ergic interneurons that express µ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of adverse effects and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, unique 'herbs" as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction.
  2. Co-Morbid Erectile Dysfunction (ED) and Antidepressant Treatment in a Patient - A Management Challenge?
    Zainol M, Sidi H, Kumar J, Das S, Ismail SB, Hatta MH, et al.
    Curr Drug Targets, 2019;20(2):182-191.
    PMID: 28302034 DOI: 10.2174/1389450118666170315110902
    Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.
  3. Natural Polyphenols in the Treatment of Alzheimer's Disease
    Syarifah-Noratiqah SB, Naina-Mohamed I, Zulfarina MS, Qodriyah HMS
    Curr Drug Targets, 2018;19(8):927-937.
    PMID: 28356027 DOI: 10.2174/1389450118666170328122527
    Neurodegenerative disease is an incurable disease which involves the degeneration or death of the nerve cells. Alzheimer's Disease (AD) is a neurodegenerative disease discovered in 1906 by Alois Alzheimer, a German clinical psychiatrist and neuroanatomist. The main pathological hallmarks of this disease are the formation of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangle (NFT). The accumulation of the amyloid protein aggregates in the brain of AD patients leads to oxidative stress and inflammation. Other postulated reasons for the development of this disease are cholinergic depletion and excessive glutamatergic neurotransmission. The current drugs approved and marketed for the treatment of AD are cholinesterase inhibitors (ChEIs) and N-methyl-Daspartate (NMDA) receptor antagonists. The function of ChEIs is to avoid cholinergic depletion; whereas the function of NMDA receptor antagonist is to block excessive glutamatergic neurotransmission. Unfortunately, the current drugs prescribed for AD show only modest improvement in terms of symptomatic relief and delay the progression of the disease. This review will discuss about several polyphenolic compounds as potential natural treatment options for AD. Three compounds are highlighted in this review - Curcumin (Cur), Resveratrol (Rsv) and Epigallocatechin-3- gallate (EGCG). These compounds have huge potential for AD treatment, especially due to their low frequency of adverse events. However, the current conventional pharmaceutical drugs remain as the mainstay of treatment for AD.
  4. Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?
    Kumar J, Ismail Z, Hatta NH, Baharuddin N, Hapidin H, Get Bee YT, et al.
    Curr Drug Targets, 2018;19(8):907-915.
    PMID: 28494749 DOI: 10.2174/1389450118666170511144302
    In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.
  5. Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery
    Tan KX, Danquah MK, Sidhu A, Yon LS, Ongkudon CM
    Curr Drug Targets, 2018 02 08;19(3):248-258.
    PMID: 27321771 DOI: 10.2174/1389450117666160617120926
    BACKGROUND: The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability.

    OBJECTIVE: The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release.

    RESULTS: This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects.

    CONCLUSION: A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with stage-wise delivery mechanism is presented to illustrate the potential efficacy of aptamer- polymer cargos for enhanced cell targeting and drug delivery.

  6. Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways
    Ngai SC
    Curr Drug Targets, 2020;21(9):849-854.
    PMID: 32116190 DOI: 10.2174/1389450121666200302124426
    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a natural protein expressed in a wide range of tissues in our body. It is a promising anti-cancer agent due to its selective killing of cancer cells, rendering normal cells unharmed. However, resistance occurs either intrinsically or develops over the course of TRAIL treatment. In view of its specificity to cancer cells, there is a pushing need to overcome TRAIL resistance. Curcumin (Cur), a natural active constituent of turmeric, has been evidenced to have anti-cancer properties. However, it is limited by its sparing solubility and low bioavailability. Combinational therapy is one of the most frequently used strategies to overcome these limitations, which has been proved to be more effective than monotherapy by achieving synergistic effects and reducing toxicity. This review aims to discuss TRAIL and its underlying apoptotic mechanisms, the combinational treatment of Cur and TRAIL in view of their respective limitations, and the underlying apoptotic mechanisms activated by the sensitization of cancers by Cur towards TRAIL-induced apoptosis. Finally, this review discusses the research gap and the author's insight into this research area in bridging the research gap from bench to bedside.
  7. Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons
    Arunachalam M, Ramesh M, Thiagarajan V, Singla SK, Mudhol S, Muthukumar SP
    Curr Drug Targets, 2021;22(14):1688-1703.
    PMID: 33618645 DOI: 10.2174/1389450122666210222163528
    The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.
  8. Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review
    Hasanpourghadi M, Looi CY, Pandurangan AK, Sethi G, Wong WF, Mustafa MR
    Curr Drug Targets, 2017;18(9):1086-1094.
    PMID: 27033190 DOI: 10.2174/1389450117666160401124842
    Phytometabolites are functional elements derived from plants and most of them exhibit therapeutic characteristics such as anti-cancer, anti-inflammatory and anti-oxidant effects. Phytometabolites exert their anti-cancer effect by targeting multiple signaling pathways. One of the remarkable phenomena targeted by phytometabolites is the Warburg effect. The Warburg effect describes the observation that cancer cells exhibit an increased rate of glycolysis and aberrant redox activity compared to normal cells. This phenomenon promotes further cancer development and progression. Recent observations revealed that some phytometabolites could target metabolic-related enzymes (e.g. Hexokinase, Pyruvate kinase M2, HIF-1) in cancer cells, with little or no harm to normal cells. Since hyper-proliferation of cancer cells is fueled by higher cellular metabolism, phytometabolites targeting these metabolic pathways can create synergistic crosstalk with induced apoptotic pathways and sensitize cancer cells to chemotherapeutic agents. In this review, we discuss phytometabolites that target the Warburg effect and the underlying molecular mechanism that leads to tumor growth suppression.
  9. Editorial
    Sulaiman AH, Musa R
    Curr Drug Targets, 2019;20(2):145.
    PMID: 30648501 DOI: 10.2174/138945012002181203145147
  10. Editorial: Advances in Psychopharmacological Treatment
    Sulaiman AH, Musa R
    Curr Drug Targets, 2018;19(8):855.
    PMID: 29792134 DOI: 10.2174/138945011908180518113546
  11. Does Vitamin K Intake Influence High Phosphate Induced Vascular Pseudo-ossification: An Underappreciated Therapeutic Prospect in General Population?
    Thent ZC, Froemming GRA, Muid SA
    Curr Drug Targets, 2019;20(4):421-430.
    PMID: 30378497 DOI: 10.2174/1389450119666181031124430
    Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms 'vitamin K', 'vascular calcification, 'phosphate', 'transdifferentiation' and 'vascular pseudoossification'. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.
  12. Osteoporotic fracture healing: potential use of medicinal plants from the tropics
    Abdul Jalil MA, Shuid AN, Muhammad N
    Curr Drug Targets, 2013 Dec;14(14):1651-8.
    PMID: 24354586
    With improvements in living standards and healthcare, life expectancy has been increasing dramatically in most parts of the world. These situations lead to the increase in the reported cases of geriatrics-related diseases such as hypogonadal osteoporosis with skeletal fracture being the ultimate outcome, which eventually causes significant morbidity and mortality. The deficient gonadal hormones, which are the main cause of hypogonadal osteoporosis, could be substituted with hormone replacement therapy to hinder bone loss. However, the artificial hormonal therapy has been linked to grievous conditions such as breast and prostate cancers. In view of the various adverse effects associated with conventional treatment, many researchers are now focusing on finding alternative remedies from nature. This article explores the possibilities of certain medicinal plants native to Malaysia that possess androgenic and antioxidant properties to potentially be used in the treatment of fracture due to osteoporosis in ageing people.
  13. Pathogenesis of alcohol-induced osteoporosis and its treatment: a review
    Abukhadir SS, Mohamed N, Mohamed N
    Curr Drug Targets, 2013 Dec;14(13):1601-10.
    PMID: 24138635
    Osteoporosis is the most common bone disease in humans; it represents a major public health problem. This chronic disease is characterized by increase in bone fracture due to: reduced bone mass, deterioration of micro architectural and decreased bone strength, bone fragility; and bone mineral density 2.5 or more standard deviations below the normal mean. Secondary osteoporosis is a common cause of osteoporosis, and there are many underlying risk factors for osteoporosis. Chronic alcohol abuse is one of the modifiable risk factors in osteoporosis. There is evidence of correlation between chronic alcohol abuse and low bone mass. Alcohol is directly toxic to the bone; with increased incidence of fractures and complications. Although there is a paucity of studies regarding alcohol induced osteoporosis therapy, it can be classified into antiresorptive therapy and anabolic therapy. Bisphosphonates have been demonstrated to be clinically relevant to prevent bone damage associated with alcohol use while parathyroid hormone increased bone mineralization as well as bone formation in alcohol treated rats. Vitamin D supplementation could prevent bone toxicity in chronic drinkers. This review discussed the pathogenesis of alcohol-induced osteoporosis and the agents available for its treatment. Other potential therapies are also discussed.
  14. Drug delivery systems for prevention and treatment of osteoporotic fracture
    Shuid AN, Ibrahim N', Mohd Amin MC, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1558-64.
    PMID: 24200294
    Anti-osteoporotic drugs are available for treatment of osteoporosis and for preventing osteoporosis complications especially fractures. Most of the current anti-osteoporotic drugs are administered orally or parenterally to target the osteoporosis-affected bones. However, bone is a peripheral organ with limited blood supply. Therefore, the drugs delivered are exposed to various physicochemical and biological factors which affect the bioavailability of the drugs. In preclinical research, the dose of a potential anti-osteoporotic agent used in animal model may be too high for human application when administered via the conventional route of administration. The current anti-osteoporotic drugs need to be administered at higher doses to account for pharmacological interactions. However, this will expose the patients to adverse effects such as the cancer risks of postmenopausal women who took estrogen replacement therapy. There is also problem with patient compliance as anti-osteoporotic drugs may have to be taken for prolonged duration. The current deliveries of drugs need to be improved to overcome these problems. This review discussed several potential drug delivery systems which are able to contain the anti-osteoporosis drugs and release them slowly to the targeted bone. Among them are various carriers, polymers and microsponges, which may not only increase drug efficacy but also reduce adverse effects. The delivery systems allow the drugs to be administered locally at the targeted bone for longer duration, therefore reducing drug frequency and improving patient's compliance. It is hoped that these delivery systems may be applicable for the treatment of osteoporosis in the future to keep tab of the rising osteoporotic fracture incidence.
  15. Cathepsin K inhibitors: a novel target but promising approach in the treatment of osteoporosis
    Helali AM, Iti FM, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1591-600.
    PMID: 23957815
    Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.
  16. Pomegranate use to attenuate bone loss in major musculoskeletal diseases: an evidence-based review
    Shuid AN, Mohamed IN
    Curr Drug Targets, 2013 Dec;14(13):1565-78.
    PMID: 24200293
    This review explores the effects of pomegranate on the pathogenesis of bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. A systematic review of the literature was conducted to identify the relevant studies on pomegranate and osteoporosis/osteoarthritis/rheumatoid arthritis. A comprehensive search was conducted in Medline and CINAHL for relevant studies published between the years 1946 to 2012. The main inclusion criteria were research articles published in English, studies had to report the association or effect of pomegranate and these bone and joint diseases: osteoporosis, osteoarthritis or rheumatoid arthritis. The literature search identified 35 potentially relevant articles, whereby 8 met the inclusion criteria. Two animal studies, two combinations of animal and in vitro studies, three in vitro studies and one human study were included in this review. All the studies reported positive effects of pomegranate extract or juice on osteoporosis, osteoarthritis and rheumatoid arthritis. This evidence-based review highlighted the potential of pomegranate extract being used for treating bone loss in osteoporosis, osteoarthritis and rheumatoid arthritis. Further studies are required to identify the active ingredients and molecular mechanisms before controlled human observational studies are conducted to provide stronger evidence.
  17. Novel Pharmacotherapeutic Approaches in Treatment of Alcohol Addiction
    Pakri Mohamed RM, Kumar J, Ahmad SU, Mohamed IN
    Curr Drug Targets, 2018;19(12):1378-1390.
    PMID: 29788886 DOI: 10.2174/1389450119666180523092534
    In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction has been a global endeavor. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as an adjunct in combination therapy. This review article summarizes the novel pharmacotherapeutic approaches used in the treatment of alcohol addiction by focusing on the drugs, which include neramexane, gabapentin, baclofen, aripiprazole, nalmafene, and quetiapine.
  18. The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism
    Hairi HA, Shuid AN, Ibrahim N', Jamal JA, Mohamed N, Mohamed IN
    Curr Drug Targets, 2019;20(2):192-200.
    PMID: 28814228 DOI: 10.2174/1389450118666170816123740
    BACKGROUND: Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause.

    OBJECTIVE: Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition.

    RESULTS: The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review.

    CONCLUSION: The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.

  19. The Role of Atypical Antipsychotics in Sexuality: Road to Recovery in Schizophrenia
    Adam RL, Sidi H, Midin M, Zakaria H, Das S, Mat KC
    Curr Drug Targets, 2018;19(12):1402-1411.
    PMID: 28464773 DOI: 10.2174/1389450118666170502130126
    Sexuality is an important dimension in human beings as a form of expression of individuality. For many decades, sexual functioning has been a neglected area among patients suffering from schizophrenia. It was a presumption that patients with schizophrenia could be asexual and this could be secondary to overwhelming situations of delusion, hallucination, hostility and negative symptoms among others. The deficient in sexual functioning are due to innate factors, i.e. negative symptoms (apathy, avolition and amotivation) and also as a result of prefrontal dysfunction, i.e. inability to plan and execute meaningful relationship. Adverse effects of the psychopharmacological agents, especially the typical antipsychotics, e.g. dystonia, excessive sedation and hyperprolactinemia may interfere with patients' sexual activity. In this review, we highlight the neurobiology of schizophrenia in the context of understanding sexual functioning and to integrate the knowledge of dopamine-serotonin neurotransmitter's interaction and the receptors' target. Interventional approaches consist of psychopharmacological and psychosocial interventions. In the perspective of sexuality, we recommend atypical antipsychotic should be placed as the first line treatment for both drug naïve patients and also to patients who are already receiving psychopharmacological agents in consideration for a drug-switch from typical to atypical antipsychotics. Aripiprazole, clozapine, olanzapine and quetiapine exert benefits in terms of sexual functioning recovery due to their atypical mechanism of action. However, the potential adverse effect like metabolic syndrome should be adequately managed to prevent negative consequences. Psychosocial interventions, i.e. psychoeducation, destigmatization, supportive psychotherapy and psychiatric rehabilitation also play a crucial role in the management. In conclusion, restoration of sexual function is an achievable recovery target in patients with schizophrenia through these biopsycho- social interventions.
  20. A Review on the Antinociceptive Effects of Mitragyna speciosa and Its Derivatives on Animal Model
    Chin KY, Mark-Lee WF
    Curr Drug Targets, 2018;19(12):1359-1365.
    PMID: 28950813 DOI: 10.2174/1389450118666170925154025
    Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM- 15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate compounds with higher potency and lesser side-effects. Human clinical trials are required to validate the use of these compounds in clinical setting.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links