scholarly journals Additive Interaction of the Cannabinoid Receptor I Agonist Arachidonyl-2-chloroethylamide with Etomidate in a Sedation Model in Mice

2008 ◽  
Vol 108 (4) ◽  
pp. 669-674 ◽  
Author(s):  
Patrick Meybohm ◽  
Philipp-Alexander Brand ◽  
Mike Ufer ◽  
Florian Thiemann ◽  
Markus Steinfath ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Volatile Anesthetics ◽  
Sedative Effect ◽  
Additive Interaction ◽  
Isobolographic Analysis ◽  
Single Drug ◽  
Selective Agonists

Background Both propofol and volatile anesthetics have been reported to interact with the endocannabinoid system. The purpose of this study was to evaluate the effect of selective agonists for cannabinoid receptor types 1 and 2 on etomidate-induced sedation. Methods A controlled, blinded, experimental study was performed in 20 mice that received intraperitoneal injections of etomidate, the cannabinoid1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the cannabinoid2 receptor agonist JWH 133 alone, and both ACEA and JWH 133 combined with etomidate. The cannabinoid1 receptor antagonist AM 251 and the cannabinoid2 receptor antagonist AM 630 were administered 10 min before the delivery of ACEA and JWH 133, respectively. Each drug combination was applied to 6-8 mice of these 20 study animals. Sedation was monitored by a Rota-Rod (Ugo Basile, Comerio, Italy). Isobolographic analysis was used for evaluation of pharmacologic interaction. Results Single drug administration of etomidate and ACEA produced dose- and time-dependent decreased time on the Rota-Rod (P < 0.05). No sedative effect was seen after JWH 133. Etomidate-induced sedation was significantly increased and prolonged with ACEA (P < 0.05), but not with JWH 133. Isobolographic analysis revealed an additive interaction between ACEA and etomidate that was antagonized by the cannabinoid1 receptor antagonist AM 251. The cannabinoid1 receptor antagonist had no effect on etomidate alone. Conclusions Etomidate-induced sedation was increased and prolonged by activation of the cannabinoid1 receptor, but not of the cannabinoid2 receptor, in mice. However, this interaction was only additive.

Pharmacologic Interaction between Cannabinoid and either Clonidine or Neostigmine in the Rat Formalin Test

2003 ◽  
Vol 99 (3) ◽  
pp. 701-707 ◽  
Author(s):  
Myung Ha Yoon ◽  
Jeong Il Choi
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Formalin Test ◽  
Cannabinoid Receptor ◽  
Phase 1 ◽  
Antinociceptive Effect ◽  
Spinal Level ◽  
Isobolographic Analysis ◽  
Cannabinoid 1 Receptor

Background Although spinal cannabinoid receptor agonist (WIN 55,212-2) has been shown to encounter various models of pain, the role of two subtypes of cannabinoid receptor for the antinociceptive effect of cannabinoids has not been investigated at the spinal level. Spinal alpha 2 receptor agonist (clonidine) and cholinesterase inhibitor (neostigmine) are also active in the modulation of nociception. The authors examined the properties of drug interaction after coadministration of WIN 55,212-2-clonidine, and intrathecal WIN 55,212-2-neostigmine, and further clarified the role of cannabinoid 1 and 2 receptors in cannabinoid-induced antinociception at the spinal level. Methods Catheters were inserted into the intrathecal space of male Sprague-Dawley rats, and 50 microl of 5% formalin solution was injected into the hind paw to evoke the pain. Isobolographic analysis was used for evaluation of pharmacologic interaction. Results Intrathecal 55,212-2, clonidine, and neostigmine dose-dependently suppressed the flinching observed during phase 1 and 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of WIN 55,212-2-clonidine or WIN 55,212-2-neostigmine mixture in both phases. The antinociceptive effect of WIN 55,212-2 was antagonized by cannabinoid 1 receptor antagonist (AM 251) but not by cannabinoid 2 receptor antagonist (AM 630). No antinociceptive effect was seen after intrathecal administration of cannabinoid 2 receptor agonist (JWH 133). Conclusions Intrathecal 55,212-2, clonidine, and neostigmine attenuate the facilitated state and acute pain. WIN 55,212-2 interacts synergistically with either clonidine or neostigmine. The antinociception of WIN 55,212-2 is mediated through the cannabinoid 1 receptor, but not the cannabinoid 2 receptor, at the spinal level.

Interaction of GABA (A) system in the nucleus accumbens ahell with ACPA on anxiety-like behaviors in Wistar male rat

2013 ◽  
Vol 1 (1) ◽  
pp. 44
Author(s):  
Mohammad Reza Zarrindast ◽  
Hatam Ahmadi ◽  
Mohammad Nasehi
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Elevated Plus Maze ◽  
Male Rat ◽  
Gaba A ◽  
Test Parameters ◽  
Plus Maze ◽  
Selective Agonists

It has been recently reported that cannabinoid and GABA systems in the nucleus accumbens (NAc) are involved in anxiety-related behaviors. Thus the purpose of the present study is to investigate the involvement of ACPA interaction with GABA-ergic of the NAc shell in anxiolytic-like behaviors in Wistar male rat. The elevated plus maze apparatus has been used to test parameters of anxiety-like behaviors. The data demonstrated that bilateral injection of GABA (A) receptor agonist (Muscimol 0.4 μg/μl) increased % OAT. Furthermore, injection of GABA (A) receptor antagonist (Bicuculline 0.9μg/μl) increased locomotor activity. The data indicated anxiolytic-like behaviors caused by the Muscimol injection into the NAc shell. Moreover, bilateral injection of ACPA (CB1 -selective agonists; 0.025μg/μl) into the NAc shell induced anxiogenic-like behaviors. The final results showed that intra-NAc shell injection of subthreshold dose of Muscimol (0.2 μg/μl) attenuated anxiogenic-like behaviors by higher dose (0.025 μg/μl) of ACPA in the NAc shell. In addition, intra-NAc shell injection of subthreshold dose of Bicuculline (0.6 μg/μl) did not alter anxiogenic response by ACPA administration in the NAc shell. The results suggested that the activation of the NAc shell GABA (A) receptor attenuated the activity of cannabinoid system in the NAc shell.

scholarly journals Cannabinoid and Kappa Opioid Receptors Reduce Potassium K Current via Activation of Gs Proteins in Cultured Hippocampal Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2356-2364 ◽  
Author(s):  
Robert E. Hampson ◽  
Jian Mu ◽  
Sam A. Deadwyler
Keyword(s):  
Protein Kinase ◽  
Receptor Antagonist ◽  
Hippocampal Neurons ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Cb1 Receptor ◽  
Kappa Opioid ◽  
K Current ◽  
Kappa Receptor ◽  
Cultured Hippocampal Neurons

The current study showed that potassium K current ( I K), which is evoked at depolarizing potentials between −30 and +40 mV in cultured hippocampal neurons, was significantly reduced by exposure to the CB1 cannabinoid receptor agonist WIN 55,212-2 (WIN-2). WIN-2 (20–40 nM) produced an average 45% decrease in I K amplitude across all voltage steps, which was prevented by SR141716A, the CB1 receptor antagonist. The cannabinoid receptor has previously been shown to be Gi/o protein-linked to several cellular processes; however, the decrease in I Kwas unaffected by modulators of Gi/o proteins and agents that alter levels of protein kinase A. In contrast, CB1 receptor-mediated or direct activation of Gsproteins with cholera toxin (CTX) produced the same decrease in I K amplitude as WIN-2, and the latter was blocked in CTX-treated cells. Gs protein inhibition via GDPβS also eliminated the effects of WIN-2 on I K. Consistent with this outcome, activation of protein kinase C (PKC) by arachidonic acid produced similar effects to WIN-2 and CTX. Kappa opioid receptor agonists, which also reduce I K amplitude via Gs proteins, were compared with WIN-2 actions on I K. The kappa receptor agonist U50,488 reduced I K amplitude in the same manner as WIN-2, while the kappa receptor antagonist, nor-binaltorphimine, actually increased I K amplitude and significantly reduced the effect of co-administered WIN-2. The results indicate that CB1 and kappa receptor activation is additive with respect to I K amplitude, suggesting that CB1 and kappa receptors share a common Gs protein signaling pathway involving PKC.

Rimonabant—A Selective CB1 Antagonist

2005 ◽  
Vol 39 (4) ◽  
pp. 684-690 ◽  
Author(s):  
Steven Thomas Boyd ◽  
Brad Allen Fremming
Keyword(s):  
Metabolic Syndrome ◽  
Smoking Cessation ◽  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Caloric Intake ◽  
Endocannabinoid System ◽  
Positive Role ◽  
Medline Search ◽  
Review Articles ◽  
Treatment Of Obesity

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of rimonabant, a new selective cannabinoid receptor antagonist. DATA SOURCES: Primary literature and review articles were obtained via a MEDLINE search (1966–November 2004) using the key terms obesity, smoking cessation, cannabinoid, rimonabant, SR 141716, and SR 141716a. Additional studies and abstracts were identified from the bibliographies of reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles related to rimonabant and the endocannabinoid system were reviewed. Data pertinent to this article were included. DATA SYNTHESIS: Rimonabant is a selective cannabinoid receptor antagonist. Recent data have demonstrated beneficial effects of rimonabant in obesity, smoking cessation, and metabolic syndrome. Animal studies using rimonabant have shown a positive role for reducing hunger, caloric intake, and body weight and in increasing satiety. In humans, rimonabant appears to be effective for treatment of obesity and smoking cessation. Ongoing studies will examine the effect of rimonabant on obesity, metabolic syndrome, smoking cessation, and alcohol abuse. To date, the incidence of adverse effects with rimonabant has been slightly greater than placebo, with the most common being nausea. CONCLUSIONS: Rimonabant appears to be a promising drug in an entirely new class called selective cannabinoid CB1 receptor antagonists. The drug may be approved for treatment of obesity and smoking cessation in 2005. Additional studies are ongoing that may provide information on other clinical uses for this medication.

scholarly journals Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion

2008 ◽  
Vol 199 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Marco Aurélio Liberato Costa da Veiga ◽  
Flávia Fonseca Bloise ◽  
Ricardo Henrique Costa-e-Sousa ◽  
Luana Lopes Souza ◽  
Norma Aparecida dos Santos Almeida ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
Male Rats ◽  
Acute Effects ◽  
Serum Tsh

We examined the acute effects of endocannabinoid, anandamide, and of synthetic cannabinoid receptor antagonist, AM251[N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], on TSH, thyroxine (T4), and triiodothyronine (T3) secretions. Euthyroid male rats showed a 42% decrease in serum TSH, 2 h after a single i.p. injection of 0.02, but not 0.2 mg/kg body weight (BW), anandamide, accompanied by a 39% reduction in serum T4, without alteration in serum T3. At 0.5 and 1 h, these serum hormones showed no significant change. Hypothyroid rats showed a 35% reduction in serum TSH (P<0.01), 2 h after anandamide injection, which had no effect on hyperthyroid rats. In both thyroid states, no modification of serum thyroid hormones was observed. Intraperitoneal injection of 0.17 or 1.7 mg/kg BW AM251 in euthyroid rats caused, 1.5 h later, 1.7-fold or 4.3-fold increase in serum TSH respectively, without changing thyroid hormones. Stimulatory effect of 0.17 mg/kg BW AM251 and inhibitory effect of anandamide was abolished in the group injected with AM251 followed by an anandamide injection, 30 min later. Intracerebroventricular injection of 20 ng (but not 200 ng) anandamide induced a decrease in serum TSH at 60 min after injection, which tended to disappear at 120 min. Anterior pituitary explants presented significant reduction in TSH release in the presence of 10−7 M anandamide in incubation medium, which was blocked by 10−7 M AM251. In conclusion, anandamide has the ability to acutely inhibit TSH release in eu- and hypothyroid rats, acting at the hypothalamus–pituitary axis. Since, in addition, the cannabinoid receptor antagonist AM251 increased TSH release, we suggest that endocannabinoid system has a role as negative regulator of TSH secretion.

Sign in / Sign up

Export Citation Format

Share Document