scholarly journals Prospects for the Use of Cannabinoid Receptor Ligands for the Treatment of Metabolic Syndrome and Atherosclerosis: Analysis of Experimental and Clinical Data

2017 ◽  
Vol 72 (1) ◽  
pp. 59-65 ◽  
Author(s):  
L. N. Maslov ◽  
R. S. Karpov
Keyword(s):  
Metabolic Syndrome ◽  
Cannabinoid Receptor ◽  
Glycosylated Hemoglobin ◽  
Experimental Studies ◽  
Blood Lipid ◽  
Cb1 Receptors ◽  
Cb2 Receptor ◽  
Receptor Agonists ◽  
Antiatherogenic Effect ◽  
Patients With Diabetes

An antagonist of central cannabinoid CB1 receptors rimonabant causes weight loss in patients with obesity and metabolic syndrome, improves blood lipid parameters, increases the adiponectin level, decreases the rate of glucose and glycosylated hemoglobin in patients with diabetes mellitustype-2. However, rimonabant adverse effects include depression, anxiety, nausea, and dizziness which are apparently due to the blockade of central CB1 receptors. In mice with a high-calorie diet, we defined that the blockade of peripheral CB1 receptors prevents obesity, steatosis of the liver, improves lipid and carbohydrate metabolism. Experimental studies suggest that peripheral CB2 receptor agonists have antiatherogenic effect. To validate the expediency of clinical research of CB2 receptor agonists in patients with atherosclerosis the comparative analysis of antiatherogenic properties of cannabinoids should be performed. In addition, experiments are needed on the combination use of cannabinoids with well-known antiatherogenic agents, such as statins.

The Cannabinoid Agonist WIN55,212-2 Suppresses Opioid-induced Emesis in Ferrets

2001 ◽  
Vol 94 (5) ◽  
pp. 882-887 ◽  
Author(s):  
Isabelle I. Simoneau ◽  
Maged S. Hamza ◽  
Heriberto P. Mata ◽  
Erin M. Siegel ◽  
Todd W. Vanderah ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Cb1 Receptors ◽  
Cb2 Receptor ◽  
Selective Antagonist ◽  
Receptor Agonists ◽  
Antiemetic Activity ◽  
The Central Nervous System ◽  
Cannabinoid Agonist

Background Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. Methods Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. Results Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WIN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. Conclusions These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

The Endocannabinoid System and Alcohol Dependence: Will Cannabinoid Receptor 2 Agonism be More Fruitful than Cannabinoid Receptor 1 Antagonism?

2021 ◽  
Vol 20 ◽  
Author(s):  
Aboagyewaah Oppong-Damoah ◽  
Brenda Marie Gannon ◽  
Kevin Sean Murnane
Keyword(s):  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Health Concern ◽  
Cb2 Receptor ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Clinical Phase ◽  
Anti Inflammatory ◽  
Cb1 Antagonists ◽  
Psychiatric Side Effects

: Alcohol-use disorder (AUD) remains a major public health concern. In recent years, there has been a heightened interest in components of the endocannabinoid system for the treatment of AUD. Cannabinoid type 1 (CB1) receptors have been shown to modulate the rewarding effects of alcohol, reduce the abuse-related effects of alcohol, improve cognition, exhibit anti-inflammatory, and neuroprotective effects, which are all favorable properties of potential therapeutic candidates for the treatment of AUD. However, CB1 agonists have not been investigated for the treatment of AUD because they stimulate the motivational properties of alcohol, increase alcohol intake, and have the tendency to be abused. Preclinical data suggest significant potential for the use of CB1 antagonists to treat AUD; however, a clinical phase I/II trial with SR14716A (rimonabant), a CB1 receptor antagonist/inverse agonist showed that it produced serious neuropsychiatric adverse events such as anxiety, depression, and even suicidal ideation. This has redirected the field to focus on alternative components of the endocannabinoid system, including cannabinoid type 2 (CB2) receptor agonists as a potential therapeutic target for AUD. CB2 receptor agonists are of particular interest because they can modulate the reward pathway, reduce abuse-related effects of alcohol, reverse neuroinflammation, improve cognition, and exhibit anti-inflammatory and neuroprotective effects, without exhibiting the psychiatric side effects seen with CB1 antagonists. Accordingly, this article presents an overview of the studies reported in the literature that have investigated CB2 receptor agonists with regards to AUD and provides commentary as to whether this receptor is a worthy target for continued investigation.

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 1: Discovery of CB2 receptor selective compounds

2007 ◽  
Vol 17 (14) ◽  
pp. 4030-4034 ◽  
Author(s):  
Hiroyuki Kai ◽  
Yasuhide Morioka ◽  
Takami Murashi ◽  
Koichi Morita ◽  
Satomi Shinonome ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Cb2 Receptor ◽  
Receptor Agonists ◽  
New Class

Inhibition of Inflammatory Hyperalgesia by Activation of Peripheral CB2Cannabinoid Receptors

2003 ◽  
Vol 99 (4) ◽  
pp. 955-960 ◽  
Author(s):  
Aline Quartilho ◽  
Heriberto P. Mata ◽  
Mohab M. Ibrahim ◽  
Todd W. Vanderah ◽  
Frank Porreca ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Thermal Hyperalgesia ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Cb2 Receptor ◽  
Inflammatory Hyperalgesia ◽  
Selective Antagonist ◽  
Receptor Agonists ◽  
Cb2 Receptors ◽  
Cns Effects

Background Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models. Nonselective cannabinoid receptor agonists also produce central nervous system (CNS) side effects. Agonists selective for CB2 cannabinoid receptors, which are not found in the CNS, do not produce the CNS effects typical of nonselective cannabinoid receptor agonists but do inhibit acute nociception. The authors used the CB2 receptor-selective agonist AM1241 to test the hypothesis that selective activation of peripheral CB2 receptors inhibits inflammatory hyperalgesia. Methods Rats were injected in the hind paw with carrageenan or capsaicin. Paw withdrawal latencies were measured using a focused thermal stimulus. The effects of peripheral CB2 receptor activation were determined by using local injection of AM1241. CB2 receptor mediation of the actions of AM1241 was shown by using the CB2 receptor-selective antagonist AM630 and the CB1 receptor-selective antagonist AM251. Results AM1241 fully reversed carrageenan-induced inflammatory thermal hyperalgesia when injected into the inflamed paw. In contrast, AM1241 injected into the contralateral paw had no effect, showing that its effects were local. AM1241 also reversed the local edema produced by hind paw carrageenan injection. The effects of AM1241 were reversed by the CB2 receptor-selective antagonist AM630, but not by the CB1 receptor-selective antagonist AM251. AM1241 also inhibited flinching and thermal hyperalgesia produced by hind paw capsaicin injection. Conclusions Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.

scholarly journals Clinicl Value of Combined Detection of Glycosylated Hemoglobin and Various Biochemical Indicators of Blood lipid, Blood glucose and Renal Function

2017 ◽  
Vol 1 (3) ◽  
Author(s):  
Lv Fengpeng
Keyword(s):  
Blood Glucose ◽  
Glycosylated Hemoglobin ◽  
Blood Lipid ◽  
Cerebrovascular Diseases ◽  
Diabetic Microangiopathy ◽  
Lesion Group ◽  
Diabetic Patients ◽  
Biochemical Indicators ◽  
Significant Difference ◽  
Patients With Diabetes

Objective: To explore the clinical values of detection results ofglycosylated hemoglobin, blood lipid, blood glucose and renalfunctions and their correlation in diabetic microangiopathy andincidence of cardiovascular and cerebrovascular diseases.Methods: The determinations of glycosylated hemoglobin(HbA1c), fasting plasma glucose (FPG), Urea, creatinine (Cr),total cholesterol (TC), triglycerides (TG), and low-densitylipoprotein cholesterol (LDL-C) were carried out in 96 cases ofdiabetic patients (divided into non-lesion group (50 cases) and non-lesion group (46 cases) according to microangiopathy status) and116 non-diabetic patients with cardiovascular and cerebrovasculardiseases (60 cases of coronary artery diseases and 56 cases ofhypertension) and the correlation of HbA1c with variousbiochemical indicators. Results: in patients with diabetes, theHbA1c with various biochemical indicators of the lesion groupsaw different levels of increases compared with the non-lesiongroup and there is statistically significant difference (P<0.05); theHbA1c and FPG, Urea, TC,TG and LDL-C of the group of non-diabetic cardiovascular and cerebrovascular diseases show apositive correlation (P<0.05). Conclusion: The joint detection ofHbA1c and various biochemical indicators is of great significanceto the diagnosis and treatment of diabetic microangiopathy andcardiovascular and cerebrovascular diseases.

Good Glycemic Control for a Low Cardiovascular Risk in Children Suffering from Diabets

2017 ◽  
Vol 68 (2) ◽  
pp. 358-361
Author(s):  
Camelia Busila ◽  
Mariana Cretu Stuparu ◽  
Aurel Nechita ◽  
Camelia Ana Grigore ◽  
Gabriela Balan
Keyword(s):  
Glycosylated Hemoglobin ◽  
Control Group ◽  
Sex Distribution ◽  
Good Glycemic Control ◽  
Rural And Urban ◽  
Lipid Panel ◽  
Patients With Diabetes ◽  
Kolmogorov Smirnov ◽  
Low Cardiovascular Risk

The study is a prospective and operational one, ant its was conducted on 58 patients with diabetes type 1 and 2. The patients sex distribution was homogenious and they come from both rural and urban environment. The statistical analisys was carried out using the programme SPSS 17.0 for Windows. The distribution normality was cheked using the Kolmogorov - Smirnov Z test. he values of glycemia, glycosylated hemoglobin, lipid panel, blood pressure have been measured and compared to the ones belonging to the control group.

TA-65, A Telomerase Activator improves Cardiovascular Markers in Patients with Metabolic Syndrome

2018 ◽  
Vol 24 (17) ◽  
pp. 1905-1911 ◽  
Author(s):  
Maria Luz Fernandez ◽  
Minu Sara Thomas ◽  
Bruno S. Lemos ◽  
Diana M. DiMarco ◽  
Amanda Missimer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Plasma Lipids ◽  
Disease Risk ◽  
Glycosylated Hemoglobin ◽  
Cardiovascular Disease Risk ◽  
Hdl Cholesterol ◽  
Double Blind ◽  
Tnf Α ◽  
Luminex Technology

Background: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending lifespan. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). Methods: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, CReactive Protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by the use of spectroscopy. Results: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p< 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. Conclusion: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

scholarly journals International randomised controlled trial evaluating metabolic syndrome in type 2 diabetic cigarette smokers following switching to combustion-free nicotine delivery systems: the DIASMOKE protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e045396
Author(s):  
Arkadiusz Krysinski ◽  
Cristina Russo ◽  
Sarah John ◽  
Jonathan D Belsey ◽  
Davide Campagna ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Delivery Systems ◽  
Ambulatory Setting ◽  
Cigarette Smokers ◽  
Nicotine Delivery ◽  
Patients With Diabetes ◽  
Type 2 Diabetic

IntroductionReducing exposure to cigarette smoke is an imperative for public health and for patients with diabetes. Increasingly, combustion-free nicotine delivery systems (C-F NDS) such as e-cigarettes and heated tobacco products are substituting conventional cigarettes and accelerating the downward trends in smoking prevalence. However, there is limited information about the long-term health impact in patients with diabetes who use C-F NDS. This randomised trial of type 2 diabetic cigarette smokers will test the hypothesis that following a switch from conventional cigarettes to C-F NDS a measurable improvement in metabolic syndrome (MetS) factors will be shown over the course of 2 years.Methods and analysisThe study is multicentre and thus will take place in five locations in four countries in an ambulatory setting. A total of 576 patients with diabetes will be randomised (1:2 ratio) to either a control arm (Study Arm A), in which they will be offered referral to smoking cessation programmes or to an intervention arm (Study Arm B) assigned to C-F NDS use. Participants will be at least 23 years old and of any gender. Patient recruitment will start in February 2021 and is expected to be completed by December 2021. Primary outcome measures include fasting plasma glucose, blood pressure, triglycerides, high-density lipoprotein and waist circumference, while secondary feature absolute change in the sum of the individual factors of MetS and change in each individual factor of MetS measured at each study time point.Ethics and disseminationThe approval of research ethics committee (REC) regarding the trial protocol, informed consent forms and other relevant documents is required to commence the study. Substantial amendments to the study protocol cannot be implemented until the REC grants a favourable opinion. The results of the study are intended to be published as articles in high quality peer-reviewed journals and disseminated through conference papers.Trial registration numberNCT04231838. Pre-results stage.

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