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.

ChemInform ◽  
2007 ◽  
Vol 38 (46) ◽  
Author(s):  
Hiroyuki Kai ◽  
et al. et al.
Keyword(s):  
Cannabinoid Receptor ◽  
Cb2 Receptor ◽  
Receptor Agonists ◽  
New Class

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

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.

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 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.

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.

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

2007 ◽  
Vol 17 (14) ◽  
pp. 3925-3929 ◽  
Author(s):  
Hiroyuki Kai ◽  
Yasuhide Morioka ◽  
Minoru Tomida ◽  
Tadashi Takahashi ◽  
Maki Hattori ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Agonists ◽  
New Class ◽  
Orally Bioavailable

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs

2008 ◽  
Vol 18 (24) ◽  
pp. 6444-6447 ◽  
Author(s):  
Hiroyuki Kai ◽  
Yasuhide Morioka ◽  
Yuji Koriyama ◽  
Kazuya Okamoto ◽  
Yasushi Hasegawa ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Receptor Agonists ◽  
New Class

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 Modulation of human T-type calcium channels by synthetic cannabinoid receptor agonists in vitro

2021 ◽  
Vol 187 ◽  
pp. 108478
Author(s):  
Chris Bladen ◽  
Somayeh Mirlohi ◽  
Marina Santiago ◽  
Mitchell Longworth ◽  
Michael Kassiou ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Cannabinoid Receptor ◽  
Synthetic Cannabinoid ◽  
Receptor Agonists ◽  
Synthetic Cannabinoid Receptor Agonists
Sign in / Sign up

Export Citation Format

Share Document