Current Drug Research Reviews - Volume 14, Issue 3, 2022

Background: Methamphetamine (METH) is classified as a Schedule II stimulant drug under the United Nations Convention on Psychotropic Substances of 1971. METH and other amphetamine analogues (AMPHs) are powerful addictive drugs. Treatments are needed to treat the symptoms of METH addiction, chronic METH use, and acute METH overdose. No effective treatment for METH abuse has been established because alterations of brain functions under the excessive intake of abused drug intake are largely irreversible due in part to brain damage that occurs in the course of chronic METH use. Objective: Modulation of brain histamine neurotransmission is involved in several neuropsychiatric disorders, including substance use disorders. This review discusses the possible mechanisms underlying the therapeutic effects of histamine H3 receptor antagonists on symptoms of methamphetamine abuse. Conclusion: Treatment of mice with centrally acting histamine H3 receptor antagonists increases hypothalamic histamine contents and reduces high-dose METH effects while potentiating lowdose effects via histamine H3 receptors that bind released histamine. On the basis of experimental evidence, it is hypothesized that histamine H3 receptors may be an effective target for the treatment METH use disorder or other adverse effects of chronic METH use.

Lung cancer is the second leading cancer with a high rate of mortality. It can be treated using different intervention techniques such as chemotherapy, radiation therapy, surgical removal, and photodynamic therapy. All of these interventions lack specificity, implying that it harms the normal cells adjacent to the infected ones. Nanotechnology provides a promising solution that increases the bioavailability of anticancer drugs at the tumor site with reduced toxicity and improved therapeutic efficacy. Nanotechnology also improves the way lung cancer is diagnosed and treated. Various nanocarriers like liposomes, polymeric nanoparticles, magnetic nanoparticles, and different theranostic approaches are already approved for medical use, while various are under clinical and preclinical stages. This review article covers the details about lung cancer, types of overexpressed receptors, and cutting-edge nanocarriers used for treating lung cancer at its specific target.

Colorectal cancer (CRC) is common cancer that is one of the leading causes of cancerrelated deaths around the world. The creation of new biomarkers for this disease is an important public health strategy for lowering the disease's mortality rate. According to new research, exosomes may be important sources of biomarkers in CRC. Exosomes are nanometer-sized membrane vesicles (30-200 nm) secreted by normal and cancer cells that transport RNA and proteins between cells and are thought to help with intercellular communication. Exosomes have been linked to CRC initiation and progression, and some differentially expressed RNAs and proteins in exosomes have been identified as potential cancer detection candidates. As a result, studying the relationship between exosomes and CRC may aid in the development of new biomarkers for the disease. This article discusses the importance of exosomes as biomarkers in the diagnosis of CRC, as well as their use in the treatment of CRC metastasis, chemoresistance, and recrudescence. The benefits and drawbacks of using exosomes as tumour markers are also discussed.

Background: COVID-19, first detected in Wuhan, China, has evolved into a lifethreatening pandemic spread across six continents, with the global case count being more than 243 million, and mortality over 4.95 million, along with causing significant morbidity. It has initiated an era of research on repurposed drugs such as hydroxychloroquine, lopinavir/ritonavir, corticosteroids, remedesivir, ivermectin, alongside selective antivirals to treat or prevent COVID- 19. Molnupiravir is an orally available emerging antiviral drug considered highly promising for COVID-19. Methods and Results: We have performed a scoping review for the use of molnupiravir against SARS-CoV-2 and COVID-19. It acts by inhibiting RNA-dependent RNA polymerase (RdRp), and exhibits broad-spectrum antiviral activity. Preclinical studies have evaluated the therapeutic efficacy as well as prophylactic activity of molnupiravir against SARS CoV-2 in various animal models that include ferrets, hamsters, mice, immunodeficient mice implanted with human lung tissue and cell cultures, in various doses ranging from 5-300 mg/kg, and results have been encouraging. Initial evidence of safety and efficacy from early phase clinical studies has been encouraging too, and recent results from a large phase 3 global trial have shown significant benefits among symptomatic outpatients. Other late-phase clinical trials are still underway with the aim of establishing molnulpiravir as a therapeutic option for COVID-19, particularly for non-hospitalized patients. Conclusion and Relevance: On the basis of the limited evidence available as of now, molnupiravir could prove to be a promising oral therapy, worthy of further exploration of its utility for both treatment and prevention of COVID-19 in humans. Elaborate clinical evaluation is further warranted to confirm whether the results are replicable to the clinical scenario among outpatients to reduce the chance of progression to more severe disease.

Diacerein (DCN), an analogue of rhein (a glycosidal compound of natural origin), is currently used in the treatment of osteoarthritis and is given a fast-track designation for development to treat epidermolysis bullosa (EB). It is a nonsteroidal anti-inflammatory drug having disease-modifying properties in osteoarthritis and anti-inflammatory effects for the treatment of EB. Diacerein has a beneficial effect on pain relief and demonstrated antioxidant and anti-apoptotic effects, which are useful in renal disease, diabetes, and other disorders. This review discusses the possible mechanism of diacerein in the management of pain. The potential role of rhein and diacerein in the treatment of neuropathic, inflammatory and nociceptive pain is also reviewed. The effect of diacerein and rhein on mediators of pain, such as transient receptor potential cation channel subfamily V (TRPV1), Substance P, glutamate, inflammatory cytokines, nitric oxide, matrix metalloproteinases, histamine, palmitoylethanolamide, nuclear factor-kappa B (NFkB), and prostaglandin, has also been discussed. The data highlights the role of diacerein in neuropathic, nociceptive and inflammatory pain. Clinical trials and mechanism of action studies are needed to ascertain the role of diacerein, rhein or their analogues in the management of pain, alone or in combination with other approved therapies.

Background: Biochanin-A (5,7 dihydroxy 4 methoxy isoflavone) is a phytochemical phytoestrogen that is highly effective against various diseases. Biochanin-A is a nutritional and dietary isoflavonoid naturally present in red clover, chickpea, soybeans and other herbs. Biochanin- A possesses numerous biological activities. Objective: The study focused on collective data of therapeutic activities of Biochanin-A. Methods: According to the literature, biochanin-A revealed a range of activities starting from chemoprevention, by hindering cell growth, activation of tumor cell death, hampering metastasis, angiogenic action, cell cycle regulation, neuroprotection, by controlling microglial activation, balancing antioxidants, elevating the neurochemicals, suppressing BACE-1, NADPH oxidase hindrance to inflammation, by mitigating the MAPK and NF- ΚB, discharge of inflammatory markers, upregulating the PPAR-γ, improving the function of heme oxygenase-1, erythroid 2 nuclear factors, detoxifying the oxygen radicals and stimulating the superoxide dismutase action, and controlling its production of transcription factors. Against pathogens, biochanin-A acts by dephosphorylating tyrosine kinase proteins, obstructing gram-negative bacteria, suppressing the development of cytokines from viruses, and improving the action of a neuraminidase cleavage of caspase-3, and acts as an efflux pump inhibitor. In metabolic disorders, biochanin-A acts by encouraging transcriptional initiation and inhibition, activating estrogen receptors, and increasing the activity of differentiation, autophagy, inflammation, and blood glucose metabolism. Conclusion: Therefore, biochanin-A could be used as a therapeutic drug for various pathological conditions and treatments in human beings.

Background: HIV infection affects millions of people globally. Currently, although several drugs have brought an improvement in the quality and life expectancy of these individuals, they are accompanied by several adverse effects. Objective: To conduct a systematic review of studies examining the relationship between antiretroviral therapy (ART) uses and secondary dyslipidemia. Methods: The review followed the criteria defined by PRISMA. Only articles that completely evaluated the lipid profile were included, which consisted of total cholesterol (TC), triglycerides (TG), and LDL cholesterol (LDL-c), HDL cholesterol (HDL-c). Results: It was observed that the use of nucleoside and non-nucleoside reverse transcriptase inhibitor (NNRTI and NNRTI respectively) drugs and protease inhibitors are the most used in ART and are associated with changes in lipid profiles. The main changes observed were increases in TC, TG, and LDL-c in addition to a decrease in HDL-c. These patients had a higher risk of developing cardiovascular disease not only due to the use of therapy, but also due to the presence of other comorbidities evaluated in these studies, such as obesity, diabetes, and hypertension. The increase in age, the difference between genders, CD4 T-cell count, and viral load, were observed as risk factors for worsening dyslipidemia. Conclusion: According to the findings of this study, anti-HIV therapy is linked to dyslipidemia, which may or may not be the primary cause, and is frequently connected with a number of metabolic problems that can exacerbate the illness.

Background: Cervix preparation is one of the main steps in the onset of labor and is very important for success in initiating or inducing labor. Objective: The present study aimed at investigating the effect of evening primrose vaginal capsule on the preparation of cervix and the consequences of labor in nulliparous women. Methods: This randomized clinical trial study was conducted in 2018 on 100 nulliparous women referred to Fatemieh Hospital in Hamadan. In intervention group (50 people), one evening primrose capsule (500 mg) was used vaginally and then two hours later, another capsule was used, and placebo was used in the control group (50 people). Then, the dilatation, effacement, Bishop scores and duration of the first stage of the labor were compared in two groups after 4 hours. Statistical analysis was performed with SPSS 21. The significance level was considered to be 0.05. Results: There was a statistically significant difference in the mean score and standard deviation of dilatation, effacement of cervix, bi-shop scores and duration of the first stage of labor four hours after the intervention in the intervention and Placebo groups by controlling the effect of potential confounding factors (P <0.001). Conclusion: The results showed that the use of evening primrose vaginal capsules can reduce the length of the first stage of labor, improve Bishop score, and soften and ripen the cervix.