scholarly journals A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 44
Author(s):  
Zhuguo Liu ◽  
Zheng Yu ◽  
Shuo Yu ◽  
Cui Zhu ◽  
Mingxin Dong ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Side Effects ◽  
Motor Function ◽  
Opiate Dependence ◽  
Morphine Dependence ◽  
Lead Compound ◽  
Nr2b Subunit ◽  
High Efficacy ◽  
High Potency ◽  
Aspartate Receptor

N-methyl-D-aspartate receptor (NMDAR) antagonists have been found to be effective to inhibit morphine dependence. However, the discovery of the selective antagonist for NMDAR GluN2B with low side-effects still remains challenging. In the present study, we report a selective NMDAR GluN2B antagonist con-T[M8Q](a conantokin-T variant) that potently inhibits the naloxone-induced jumping and conditioned place preference of morphine-dependent mice at nmol/kg level, 100-fold higher than ifenprodil, a classical NMDAR NR2B antagonist. Con-T[M8Q] displays no significant impacts on coordinated locomotion function, spontaneous locomotor activity, and spatial memory mice motor function at the dose used. Further molecular mechanism experiments demonstrate that con-T[M8Q] effectively inhibited the transcription and expression levels of signaling molecules related to NMDAR NR2B subunit in hippocampus, including NR2B, p-NR2B, CaMKII-α, CaMKII-β, CaMKIV, pERK, and c-fos. The high efficacy and low side effects of con-T[M8Q] make it a good lead compound for the treatment of opiate dependence and for the reduction of morphine usage.

Small Molecular Gemcitabine Prodrugs for Cancer Therapy

2020 ◽  
Vol 27 (33) ◽  
pp. 5562-5582 ◽  
Author(s):  
He Miao ◽  
Xuehong Chen ◽  
Yepeng Luan
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drug ◽  
Drug Stability ◽  
Effective Means ◽  
Active Form ◽  
Deoxycytidine Kinase ◽  
High Efficacy ◽  
Pyrimidine Nucleoside ◽  
Design And Synthesis

Gemcitabine as a pyrimidine nucleoside analog anticancer drug has high efficacy for a broad spectrum of solid tumors. Gemcitabine is activated within tumor cells by sequential phosphorylation carried out by deoxycytidine kinase to mono-, di-, and triphosphate nucleotides with the last one as the active form. But the instability, drug resistance and toxicity severely limited its utilization in clinics. In the field of medicinal chemistry, prodrugs have proven to be a very effective means for elevating drug stability and decrease undesirable side effects including the nucleoside anticancer drug such as gemcitabine. Many works have been accomplished in design and synthesis of gemcitabine prodrugs, majority of which were summarized in this review.

LASER 532-NM ND:YAG PICOSECOND IN TREATMENT OF SOLAR LENTIGO AND EPHELIDES

2020 ◽  
pp. 72-77
Author(s):  
Ha Bui Manh ◽  
Thanh Le Thai Van
Keyword(s):  
Side Effects ◽  
Key Words ◽  
Descriptive Study ◽  
Patient Evaluation ◽  
High Efficacy ◽  
Mild Pain ◽  
Solar Lentigo ◽  
Pre Treatment ◽  
532 Nm

Aims: To evaluate the efficacy, side effects of laser 532-nm Nd:YAG picosecond in treating solar lentigo and ephelides at HCMC hospital of dermato-venereology. Objectives and Method: Prospective - descriptive study. There were 43 patients dealing with solar lentigo and ephelides treated with laser 532-nm Nd:YAG picosecond. Each patient went through 3 treatments with one month interval, three months follow up for delayed side effects and recurrent. Evaluating the treatment by MI, VLCS, self-patient evaluation with 5 grades scale. Evaluating side effects of the treatment by 5 grade Wong-Baker scale. Collected data were analysed with SPSS.20.0. Results: Based on MI at the end of the study, the effectiveness of the treatment gained 81.4% good, 16.3% average and 2.3% bad. Self-patient evaluation revealed 76.7% good, 20.9% average and 2.3% bad. VLCS of post-treatment reduced 7.44 ± 2.14 unit compares with of pre-treatment. Recently after treatment, 100% patients had erythema and mild pain in 5 grade Wong-Baker scale, 20.9% had mild edema, 2.3% had post imflammatory hyperpigmentation (PIH). Two ephelides cases recurred 3 months after treatment (4.6%). Conclusions: Laser 523-nm Nd:YAG picosecond has high efficacy and less side effects in treating solar lentigo and ephelides. Key words: solar lentigo, ephelides, laser 532-nm Nd:YAG picosecond

scholarly journals Using Oral and Intranasal Dosage Forms of Ketamine for Managing Treatment-Resistant Depression: A Review of the Literature

2016 ◽  
Vol 4 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Patrick Arthur Twohig ◽  
Vaughn Huckfeldt
Keyword(s):  
Health Care ◽  
Side Effects ◽  
Care Setting ◽  
Dosage Forms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Similar Reduction ◽  
Aspartate Receptor ◽  
Pubmed Database ◽  
Resistant Depression

A lack of effective treatment for patients with treatment-resistant depression (TRD) has led to the evaluation of ketamine, an N-methyl- D-aspartate receptor antagonist. Despite the demonstrated short-term benefits of using intravenous (IV) ketamine, side effects and the difficulty in administering ketamine outside the health-care setting has raised interest in alternative dosage forms. Research articles evaluating oral or intranasal (IN) ketamine were retrieved from the PubMed database. Patients who received oral or IN ketamine experienced a similar reduction in depressive symptoms within 24 hours of treatment and fewer side effects compared to patients who received IV ketamine. Novel administration forms of ketamine provide an opportunity for patients with TRD to achieve remission with fewer adverse side effects. Future studies should continue to evaluate these administration strategies in the hope of promoting ketamine’s use outside health-care settings and for longer time periods.

scholarly journals THE STUDY OF EFFICACY OF SUBLINGUAL MISOPROSTOL IN TERMINATION OF EARLY PREGNANCY

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Arti Kumari ◽  
Usha Kumari ◽  
Anupama Sinha
Keyword(s):  
Side Effects ◽  
Spontaneous Abortion ◽  
Early Pregnancy ◽  
Gestational Age ◽  
High Efficacy ◽  
Missed Abortion ◽  
Pregnancy Failure ◽  
Products Of Conception ◽  
Early Pregnancy Failure ◽  
Sublingual Misoprostol

Introduction: Nearly 20% of all confirmed pregnancies end in spontaneous abortion. Misoprostol’s use in early pregnancy failure is varied and dose and route are not well established. AIM: To study the efficacy of sublingual misoprostol in causing expulsion of products of conception in early pregnancy failure. Methods: Women with an ultrasound diagnosis of early pregnancy failure, less than 12 weeks gestation were included in the study. Tablet Misoprostol 600 mcg was given six hourly sublingually for 3 doses. All observations were noted and analyzed. Results: Mean gestational age was 7.946+1.2 weeks. Mean induction abortion interval was 18.241+1.2 hours. Women with gestational age six to eight weeks had least mean induction-abortion interval time of 17.38+2.86. Mean dose required was 1560mcg. Efficacy of protocol was 92.85% in achieving complete abortion. Conclusion: The regime had 92.85% efficacy, acceptability (90%) and few side effects. Thus by using a lower dose and appropriate interval between two doses (six hours), the side effects were lessened with high efficacy. Keywords: Efficacy, Missed Abortion, Misoprostol.

scholarly journals The next generation of RNA vaccines: self-amplifying RNA

2021 ◽  
Author(s):  
Anna Blakney
Keyword(s):  
Side Effects ◽  
Messenger Rna ◽  
Rapid Development ◽  
Next Generation ◽  
High Efficacy ◽  
Vaccine Platform ◽  
The Future ◽  
High Doses ◽  
The Stability

The global COVID-19 pandemic has brought tremendous momentum to the field of messenger RNA (mRNA) vaccines. The advantages of this vaccine platform, such as rapid development and high efficacy, resulted in mRNA vaccines being the first approved vaccines against COVID-19. Looking forward to the development of future vaccines, how can we make RNA vaccines even better? While improvements in the stability of the formulation and cost of the vaccine are inevitable, one of the main challenges is lowering the dose of RNA in order to avoid side effects associated with high doses of RNA. One way to do this is by using self-amplifying RNA (saRNA), a type of mRNA that encodes a replicase that copies the original strand of RNA once it’s in the cell. Here, we discuss the origins of saRNA, how it works in comparison to mRNA, current challenges in the field and the future of saRNA vaccines.

Intraventricular but not intraparaventricular nucleus metergoline elicits feeding in satiated rats

1994 ◽  
Vol 266 (5) ◽  
pp. R1562-R1567 ◽  
Author(s):  
D. V. Coscina ◽  
D. Feifel ◽  
J. N. Nobrega ◽  
P. J. Currie
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Total Dose ◽  
Paraventricular Nucleus ◽  
Dose Response ◽  
Feeding Experiment ◽  
High Potency ◽  
Drug Doses ◽  
Dose Response Study ◽  
The Brain

Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Dihydromyricetin, a Natural Flavonoid, on Morphine-induced Conditioned Place Preference and Physical Dependence in Mice

Drug Research ◽  
2020 ◽  
Vol 70 (09) ◽  
pp. 410-416
Author(s):  
Leila Etemad ◽  
Hadi Farkhari ◽  
Mohaddeseh Sadat Alavi ◽  
Ali Roohbakhsh
Keyword(s):  
Locomotor Activity ◽  
Animal Models ◽  
Conditioned Place Preference ◽  
Gabaa Receptors ◽  
Physical Dependence ◽  
Place Preference ◽  
Morphine Dependence ◽  
Male Mice ◽  
Alcohol Hangover ◽  
Withdrawal Signs

Abstract Objective Dihydromyricetin (DHM), a natural flavonoid, is used to reduce alcohol hangover. It has a modulatory role on GABAA receptors with significant effects on seizure and anxiety in animal models. We aimed to evaluate the effect of DHM on morphine conditioned place preference (CPP) and withdrawal sings following morphine dependence using animal models. Methods The effect of DHM (1, 2 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP was evaluated in male mice. Administration of morphine for three consecutive days induced physical dependence. The withdrawal signs such as jumping and defecation were precipitated by administration of naloxone (8 mg/kg, ip). The effect of DHM on the development of physical dependence was assessed by injection of DHM before morphine administrations. Results DHM, at the dose of 5 mg/kg, reduced expression of morphine CPP with an increase in the locomotor activity. DHM, at the doses of 2 and 5 mg/kg, also reduced development of morphine CPP. DHM alleviated development of morphine-induced physical dependence at the dose of 1, 2, and 5 mg/kg by decreasing jumping and defecation. Conclusion These results indicated that DHM decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.

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