Displaying publications 1 - 20 of 80 in total

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  1. Yee A, Ng CG, Seng LH
    Curr Drug Targets, 2018;19(12):1412-1423.
    PMID: 29149828 DOI: 10.2174/1389450118666171117131151
    BACKGROUND: Vortioxetine is a multimodal antidepressant that has been developed for the treatment of major depressive and anxiety disorders. The aim of this review is to quantitatively synthesize all data of the efficacy, safety and tolerability of Vortioxetine in treating anxiety disorder.

    METHOD: Terms of "Vortioxetine" OR "LuAA21004" AND "anxiety" OR "fear" OR "panic" OR "phobia" were searched. A total of two phase II and five phase III clinical trials were found.

    RESULTS: Vortioxetine was overall superior to placebo in terms of the mean change from baseline in HAM-A total score at week 8 with the pool effect size of -2.95, 95% CIs, -4.37 to -1.53, p<0.01. The patients who received 5 mg of Vortioxetine had higher response rate when compared to placebo (pooled odds ratio=1.4, 95% CI = 1.08 to 1.82, p=0.01). However, the pooled odds ratio of the HAMA remission rate was not statistically significant for both Vortioxetine and placebo (pooled odds ratio= 1.06, 95% CI = 0.86 to 1.30, p=0.62). Although the discontinuation due to adverse effects was higher in Vortioxetine than placebo group (pooled OR= 1.55, 95% CI = 1.04 to 2.31, P= 0.037), the lack of efficacy (pooled OR= 0.39, 95% CI = 0.27 to 0.57, P<0.01) was higher in placebo than Vortioxetine group. Most of the adverse effects were mild and moderate. Overall, Vortioxetine displayed a good safety and tolerability profile.

    CONCLUSION: This review supports the use of Vortioxetine for anxiety disorder. However, further longterm placebo-control observational study or a post market survey would help in strengthening the evidence for this treatment modality.

  2. Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(8):888-897.
    PMID: 28914205 DOI: 10.2174/1389450118666170913161030
    Depression is a common psychiatric disorder that decreases the quality of life and increases the mortality of patients. It incurs significant healthcare costs if left untreated. Even though intervention with antidepressants can reduce depressive symptoms, side effects are often an issue and relapse is very common. Vitamin D, commonly known as the sunshine vitamin, is an essential fat-soluble vitamin for the absorption of calcium to prevent rickets (children) and osteomalacia (adults). Evidence on a possible relationship between vitamin D deficiency and depression is growing. In this review, the authors summarized the evidence on the association between vitamin D status and depression in human observational studies, followed by clinical trials to evaluate the effects of vitamin D supplementation in treating depression. In conclusion, vitamin D deficiency may be associated with an increased risk or severity of depression. Supplementation of vitamin D may confer protection for depressed patients.
  3. Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2018;19(5):439-450.
    PMID: 26343111 DOI: 10.2174/1389450116666150907100838
    BACKGROUND: Vitamin C, traditionally associated with scurvy, is an important nutrient for maintaining bone health. It is essential in the production of collagen in bone matrix. It also scavenges free radicals detrimental to bone health.

    OBJECTIVE: This review aims to assess the current evidence of the bone-sparing effects of vitamin C derived from cell, animal and human studies.

    RESULTS: Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death. Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation. Vitamin C supplementation was able to prevent bone loss in several animal models of bone loss. Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers. Some studies suggested that the relationship between vitamin C and bone health could be U-shaped, more prominent in certain subgroups and different between dietary and supplemental form. However, most of the studies were observational, thus could not confirm causality. One clinical trial was performed, but it was not a randomized controlled trial, thus confounding factors could not be excluded.

    CONCLUSION: vitamin C may exert beneficial effects on bone, but more rigorous studies and clinical trials should be performed to validate this claim.

  4. Ibrahim N', Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(13):1524-32.
    PMID: 23876090
    Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.
  5. Yusof F, Sidi H, Das S, Midin M, Kumar J, Hatta MH
    Curr Drug Targets, 2018;19(8):856-864.
    PMID: 27993112 DOI: 10.2174/1389450117666161215161108
    Premature ejaculation (PE) is one of the commonest male sexual dysfunctions. It is characterized by ejaculation which occurs before or soon after vaginal penetration, which causes significant psychological distress to the individual, and his partner. The exact cause of PE is still unknown but several mechanisms are proposed, and these involve complex interactions of neurophysiological, psychosocial, and cognitive factors. We discuss the role of serotonin, nitric oxide, phosphodiesterase enzymes and other neurotransmitters. Treatment of PE tends to co-occur with other sexual difficulties, especially erectile dysfunction (ED). Treatment with selective serotonin reuptake inhibitors (SSRIs) and Dapoxitene are also discussed in detail. The treatment strategy requires a comprehensive holistic approach incorporating both combination of psychopharmacological agent and cognitive-behavioral therapy (CBT). The present review highlights the integration of the hypothalamic-neural and reverberating emotional circuit and discusses the etiology and treatment for patients with PE.
  6. Mohamed RMP, Kumar J, Yap E, Mohamed IN, Sidi H, Adam RL, et al.
    Curr Drug Targets, 2019;20(2):158-165.
    PMID: 28641520 DOI: 10.2174/1389450118666170622092824
    Memories associated with substance use disorders, or substance-associated cues increase the likelihood of craving and relapse during abstinence. There is a growing consensus that manipulation of synaptic plasticity may reduce the strength of substance abuse-related memories. On the biological front, there are new insights that suggest memories associated with substance use disorder may follow unique neurobiological pathways that render them more accessible to pharmacological intervention. In parallel to this, research in neurochemistry has identified several potential candidate molecules that could influence the formation and maintenance of long-term memory. Drugs that target these molecules (blebbistatin, isradipine and zeta inhibitory peptide) have shown promise at the preclinical stage. In this review, we shall provide an overview of the evolving understanding on the biochemical mechanisms involved in memory formation and expound on the premise that substance use disorder is a learning disorder.
  7. Wong SK, Chin KY, Ima-Nirwana S
    Curr Drug Targets, 2019;20(12):1264-1280.
    PMID: 30961493 DOI: 10.2174/1389450120666190405172524
    Metabolic Syndrome (MetS) involves a cluster of five conditions, i.e. obesity, hyperglycaemia, hypertension, hypertriglyceridemia and low High-Density Lipoprotein (HDL) cholesterol. All components of MetS share an underlying chronic inflammatory aetiology, manifested by increased levels of pro-inflammatory cytokines. The pathogenic role of inflammation in the development of MetS suggested that toll-like receptor (TLR) activation may trigger MetS. This review summarises the supporting evidence on the interactions between MetS and TLR activation, bridged by the elevation of TLR ligands during MetS. The regulatory circuits mediated by TLR activation, which modulates signal propagation, leading to the state of chronic inflammation, are also discussed. Taken together, TLR activation could be the molecular basis in the development of MetS-induced inflammation.
  8. Radzi NFM, Ismail NAS, Alias E
    Curr Drug Targets, 2018;19(9):1095-1107.
    PMID: 29412105 DOI: 10.2174/1389450119666180207092539
    BACKGROUND: There are accumulating studies reporting that vitamin E in general exhibits bone protective effects. This systematic review, however discusses the effects of a group of vitamin E isomers, tocotrienols in preventing bone loss through osteoclast differentiation and activity suppression.

    OBJECTIVE: This review is aimed to discuss the literature reporting the effects of tocotrienols on osteoclasts, the cells specialized for resorbing bone.

    RESULTS: Out of the total 22 studies from the literature search, only 11 of them were identified as relevant, which comprised of eight animal studies, two in vitro studies and only one combination of both. The in vivo studies indicated that tocotrienols improve the bone health and reduce bone loss via inhibition of osteoclast formation and resorption activity, which could be through regulation of RANKL and OPG expression as seen from their levels in the sera. This is well supported by data from the in vitro studies demonstrating the suppression of osteoclast formation and resorption activity following treatment with tocotrienol isomers.

    CONCLUSION: Thus, tocotrienols are suggested to be potential antioxidants for prevention and treatment of bone-related diseases characterized by increased bone loss.

  9. Azlina MFN, Qodriyah MS, Kamisah Y
    Curr Drug Targets, 2018;19(12):1456-1462.
    PMID: 29173163 DOI: 10.2174/1389450118666171122130338
    BACKGROUND: Scientific reports had shown that stress is related to numerous pathological changes in the body. These pathological changes can bring about numerous diseases and can significantly cause negative effects in an individual. These include gastric ulcer, liver pathology and neurobehavioral changes. A common pathogenesis in many diseases related to stress involves oxidative damage. Therefore, the administration of antioxidants such as vitamin E is a reasonable therapeutic approach. However, there is conflicting evidence about antioxidant supplementation.

    OBJECTIVE: The aim of this work was to summarize documented reports on the effects of tocopherol and tocotrienol on various pathological changes induced by stress.

    RESULTS AND CONCLUSION: This review will reveal the scientific evidence of enteral supplementation of vitamin E in the forms of tocotrienol and tocopherol in animal models of stress. These models mimic the stress endured by critically ill patients in a clinical setting and psychological stress in individuals. Positive outcomes from enteral feeding of vitamin E in reducing the occurrence of stress-induced pathological changes are discussed in this review. These positive findings include their ability to reduced stress-induced gastric ulcers, elevated liver enzymes and improved locomotors activity. Evidences showing tocotrienol and tocopherol effects are not just related to its ability to reduce oxidative stress but also acting on other mechanism, are discussed.

  10. Sakthiswary R, Das S
    Curr Drug Targets, 2013 Dec;14(13):1552-7.
    PMID: 23848441
    Osteoporosis is a common complication observed in rheumatoid arthritis (RA). Accelerated bone loss is always a matter of concern. The pathogenesis of RA may be important for better understanding of the bone loss. The mechanism involved in the bone loss in RA is not well understood although cytokines such as interleukin 1 and tumour necrosis factor α (TNF α) have been strongly implicated. TNF α antagonists have revolutionised the treatment of RA in the recent years. Beyond the control of disease activity in RA, accumulating evidence suggests that this form of therapy may provide beneficial effects to the bone metabolism and remodeling. An extensive search of the literature was performed in the Medline, Scopus and EBSCO databases to evaluate the documented research on the effects of TNF α antagonists in RA on bone mineral density and bone turnover markers. The available data based on our systematic review, depict a significant association between TNF α antagonists treatment and suppression of bone resorption.
  11. Andrew BN, Guan NC, Jaafar NRN
    Curr Drug Targets, 2018;19(8):877-887.
    PMID: 28322161 DOI: 10.2174/1389450118666170317162603
    BACKGROUND: One of the goals of cancer treatment is symptoms management especially at the end stage. The common symptoms in cancer include pain, fatigue, depression and cognitive dysfunction. The available treatment options for symptom management are limited. Methylphenidate, a psychostimulant, may be of benefit for these patients. In this report, we review the use of methylphenidate for symptoms control in cancer patients.

    METHOD: Electronic literature search on PubMed was conducted using the following keywords: methylphenidate, cancer, carcinoma, oncology, oncological and tumour. We identified forty two relevant studies and publications on the use of methylphenidate in cancer patients to be included in this review.

    RESULTS: Methylphenidate was found to have some evidence in reducing opioid-induced sedation, improving cognitive symptoms and reduction of fatigue in cancer patients. Nevertheless, the results were inconsistent due to variations in the study populations, study design and outcome measures, among others. There was minimal evidence on its use in treating depression. Otherwise, methylphenidate was generally well-tolerated by patients.

    CONCLUSION: This review potentially supports the use of methylphenidate for opioid-induced sedation, cognitive decline and fatigue in cancer patients. Further placebo-controlled trials would help in strengthening the evidence for this treatment.

  12. Zaini S, Guan NC, Sulaiman AH, Zainal NZ, Huri HZ, Shamsudin SH
    Curr Drug Targets, 2018;19(12):1431-1455.
    PMID: 29484993 DOI: 10.2174/1389450119666180226125026
    Cancer patients are commonly associated with various physical and psychological symptoms. In palliative setting, the aims are to relieve those symptoms, improve quality of life, and increase medication adherence among cancer patients. Antidepressants are generally accepted for the treatment of depression among patients with or without cancer. Some other potential benefits of the antidepressants have been reported in cancer patients.

    OBJECTIVE: This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients.

    RESULTS: Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients. These studies are categorised according to the hierarchy of evidence from high to low level, namely randomised controlled trials, cohort studies, case-control studies, case series, case reports, as well as other type of publications. The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression, anxiety, hot flashes and other symptoms such as sexual dysfunction, fatigue, nicotine dependence, vasomotor symptoms, executive functions, sleep problems, pruritus, as well as for hypochondriasis. While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron, mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients.

    CONCLUSION: More research studies with adequate statistical power are warranted to validate the use of antidepressants among cancer patients in treating these physical and psychological symptoms.

  13. Chakraborty C, Teoh SL, Das S
    Curr Drug Targets, 2017;18(14):1653-1663.
    PMID: 27231109 DOI: 10.2174/1389450117666160527142321
    BACKGROUND: The present era is fast experiencing rapid innovation in the genome-editing technology. CRISPR Cas9-mediated targeted genetic manipulation is an easy, cost-effective and scalable method. As a result, it can be used for a broad range of targeted genome engineering.

    OBJECTIVE: The main objective of the present review is to highlight the structural signature, classification, its mechanism and application from basic science to medicine and future challenges for this genome editing tool kit.

    RESULTS: The present review provides a brief description of the recent development of CRISPR-Cas9 genome editing technology. We discuss the paradigms shift for this next generation genome editing technology, CRISPR. The CRISPR structural significance, classification and its different applications are also being discussed. We portray the future challenges for this extraordinary genome in vivo editing tool. We also highlight the role of CRISPR genome editing in curing many diseases.

    CONCLUSION: Scientists and researchers are constantly looking one genome editing tool that is competent, simple and low-cost assembly of nucleases. It can target any particular site without any off-target mutations in the genome. The CRISPR-Cas9 has all of the above characteristics. The genome engineering technology may be a strong and inspiring technology meant for the next generation of drug development.

  14. Mohamed N, Muhammad N, Shuid AN, Soelaiman IN
    Curr Drug Targets, 2018;19(12):1424-1430.
    PMID: 28950810 DOI: 10.2174/1389450118666170925154428
    Nicotine is one of the most abused substances worldwide and can cause several harmful effects on health. One of the harmful effects, which is often ignored, is osteoporosis. Smoking has been shown to cause a decrease in bone mineral density in humans. Animal studies have proven that nicotine exerts negative effects on bone. The number of people who smoke increases each day. Those who smoke start at a very young age and they usually smoke for years. This will increase the risk of developing osteoporosis. As the prevalence of osteoporosis increases, the risk of fractures also increases. The major concerns are disability following fractures, mortality due to complications after fractures and the increasing cost of management and therapy. This paper will review the effects of nicotine on bone and the potential natural products which can be used as treatment for nicotine-induced osteoporosis.
  15. 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.
  16. Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.
    Curr Drug Targets, 2023;24(8):627-647.
    PMID: 37291783 DOI: 10.2174/1389450124666230608150759
    The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
  17. Koon CS, Sidi H, Kumar J, Xi OW, Das S, Hatta MH, et al.
    Curr Drug Targets, 2018;19(12):1366-1377.
    PMID: 28215172 DOI: 10.2174/1389450118666170215164747
    Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually initiates orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in this context and constitutes a therapeutic challenge. PDE-5i work via the dopaminergic-oxytocin-nitric oxide pathway by increasing the availability of endothelial's guanosine monophosphate (GMP), immediately causing relaxation of the penile smooth muscle and an erection. The PDE-5i, like sildenafil, vardenafil and tadalafil, are effective in the treatment of ED with some benefits/ flexibilities and disadvantages compared to other treatment modalities. Prescribed PDE-5i exclusively improve EF, fostering male's self-confidence and self-esteem. Treatment failures are associated with factors such as absent (or insufficient) sexual stimulation, psychosexual conflicts and the co-existence of medical disorders. Managing ED requires dealing with underlying medical diseases, addressing other co-morbid sexual dysfunctions like premature ejaculation (PE), and educating the patient on healthy life-styles. Furthermore, by dealing with interpersonal dynamics within the couple and embracing adequate lifestyles (managing stress and revising one's sexual scripts), PDE-5i treatment benefits may be enhanced. In this review, we propose a holistic conceptual framework approach for psychiatric management of patients with ED.
  18. Deang KT, Sidi H, Zakaria H, Adam RL, Das S, Hatta NH, et al.
    Curr Drug Targets, 2019;20(2):210-219.
    PMID: 28494748 DOI: 10.2174/1389450118666170511145628
    Attention deficit hyperactive disorder (ADHD), a hyperactivity disorder prevalent among children may continue as an adulthood attention deficit. To date, treating an individual with an adult ADHD may be an arduous task as it involves numerous challenges, which include a need for high index of suspicion to diagnose this medical condition. Many psychiatric disorders masquerade as ADHD and delay the necessary assessment and proper treatment for this debilitating medical disorder. Adult ADHD is often misdiagnosed (or under diagnosed) due to the fact that this medical condition is being masked by the patients' high level of intellectual achievement. As the ADHD in adult persists, it may end-up with impairment in the personal-social-occupational function in which the management becomes a great challenge. The treatment of ADHD can be optimized by using various drugs targets agents like norepinephrine-dopamine reuptake inhibitor (NDRI), with or without psycho stimulants like methylphenidate, which is marketed as Ritalin. Bupropion, an NDRI has a novel effect on ADHD as the molecule exerts its effects by modulating the reward-pleasure mesolimbic dopaminergic system and at the same time regulates the elevating mood dimension of the noradrenergic neurotransmission. The role of Bupropion in the neural and psychopharmacological perspective treatment of ADHD was deliberated. The present review highlights the novel effects of Bupropion in ADHD treatment, together with the help of other successful bio-psycho-social measures. This may be of immense benefit to the psychiatrists for treating their patients.
  19. Kadir ZS, Sidi H, Kumar J, Das S, Midin M, Baharuddin N
    Curr Drug Targets, 2018;19(8):916-926.
    PMID: 28228081 DOI: 10.2174/1389450118666170222153908
    Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD). In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant challenge to the medical and health professionals due to the very demanding needs in health care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho- social processes, involving bidirectional connections between pelvic-genital (local) and higher mental function (central regulation). It has robust neural and psychological-cognitive loop feedback involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e. both "quick threat assessment" of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review, a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science which demands a better and deeper understanding on the clinico-pathological correlation to enhance an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the current core knowledge in the perspective of neuroscience.
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