Disease relevance of LMFA08020040

• Activation of CB1r by the agonists (delta)(9)-tetrahydrocannabinol, WIN 55,212-2, and methanandamide inhibited emesis and their action was reversed by a selective CB1r antagonist, which alone had no effect, but potentiated vomiting in response to an emetic stimulus [1].
• Pretreatment of aortic rings with pertussis toxin attenuated the methanandamide-induced vasorelaxation in endothelium-intact aortic rings, indicating the involvement of G(i/o) proteins in the vasorelaxation; however, pertussis toxin treatment failed to block the endothelium-independent response [2].
• Following this bradycardia and hypotension (presumably evoked by the Bezold-Jarisch reflex; phase I), capsaicin, anandamide and methanandamide led to a brief vasopressor effect (phase II) [3].
• In conclusion, the endogenous cannabinoid receptor agonist anandamide and its stable analogue methanandamide induce reflex bradycardia and hypotension (phase I) by activating the vanilloid VRI receptor [3].
• Methanandamide increases COX-2 expression and tumor growth in murine lung cancer [4].

High impact information on LMFA08020040

• Hypotonic reduction of AQP5 was blocked by ruthenium red, methanandamide, and miconazole, agents that inhibit the cation channel transient receptor potential vanilloid (TRPV) 4 present in lung epithelial cells [5].
• Finally, immunohistochemical analyses by confocal microscopy revealed that adult neurogenesis in dentate gyrus was significantly decreased by the AEA analogue methanandamide and increased by the CB(1) antagonist SR141716 [6].
• Comparable results were obtained with the more stable anand-amide derivative methanandamide (20 microM; 20 +/- 2% decrease in WT; 4 +/- 6% increase in TASK-1-/-) [7].
• Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans [8].
• However, methanandamide-treated cells showed a 12-fold increase in claudin-5 expression and a 2- to 3-fold increase in claudin-3, consistent with the notion that specific changes in claudin expression levels may correlate with changes in alveolar epithelial barrier function [9].

Chemical compound and disease context of LMFA08020040

• Consistent with these results, methanandamide increased PGE2 and COX-2 levels in murine lung cancer cells in vitro via a cannabinoid receptor-independent mechanism [4].

Biological context of LMFA08020040

• Methanandamide did not alter cell viability [9].
• Non-endothelium-dependent vasorelaxation was observed to be a maximum of 20-22% at >10 microM methanandamide [2].
• Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries [10].
• The second goal of this study was to investigate whether the FAAH inhibitor OL-135 (1-oxo-1[5-(2-pyridyl)-2-yl]-7-phenylheptane), anandamide, other FAAs, and methanandamide would affect working memory in both genotypes [11].
• It is concluded that methanandamide depresses intestinal peristalsis via activation of CB1 receptors on enteric neurons, which results in blockade of excitatory motor pathways and facilitation of inhibitory pathways operating via apamin-sensitive K+ channels and nitric oxide [12].

Anatomical context of LMFA08020040

• 1. We have shown that the endocannabinoid anandamide and its stable analogue methanandamide relax rings of rabbit superior mesenteric artery through endothelium-dependent and -independent mechanisms that are unaffected by blockade of NO synthase and cyclooxygenase [13].
• 5. Methanandamide failed to relax carotid arteries pre-contracted with phenylephrine, but inhibited forskolin-induced relaxation of these arteries [14].
• Like C-PAF, methanandamide evoked spontaneous activity in quiescent myocytes [15].
• WIN55212-2, methanandamide, and Delta(9)-THC also were assayed for the inhibition of adenylyl cyclase in cerebellar membranes [16].
• 1. The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro [17].

Associations of LMFA08020040 with other chemical compounds

• METHODS: A metabolically stable analog of AEA, methanandamide (MethA, 300 nmol/kg per min), was infused into the left renal medulla of anesthetized Wistar rats with or without a selective TRPV1 antagonist, capsazepine (Capz, 150 nmol/kg per min) or a selective cannabinoid receptor 1 (CB1) antagonist, AM251 (Am, 150 nmol/kg per min) [18].
• These data show that capsaicin and ruthenium red attenuate vasorelaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arterial segments [19].
• The efficacious CB(1) receptor analogs desacetyllevonantradol (10 microM) and WIN55212-2 (10 microM) failed to produce vasorelaxation; however, the endothelium-dependent vasorelaxation evoked by methanandamide was partially (75%) blocked by the CB(1) receptor antagonist SR141716A [2].
• Smooth muscle cells of third to fourth order branches of the mesenteric artery, which have a more negative resting membrane potential and show smaller responses to acetylcholine, hyperpolarized by about 6 mV to both anandamide and methanandamide, whereas another CB(1) receptor agonist, WIN 55,212-2, had no effect [10].
• The CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) blocked the effects of Delta(9)-THC, but not those of methanandamide [20].

Gene context of LMFA08020040

• Methanandamide, which is not metabolized by FAAH, disrupted working memory performance in both genotypes (ED(50) = 10 mg/kg), suggesting that CB(1) receptor signaling is unaltered by FAAH deletion [11].
• These results suggest that methanandamide augments tumor growth by a cannabinoid receptor-independent pathway that is associated with the up-regulation of COX-2 [4].
• Radioimmunoassay showed that methanandamide increased plasma calcitonin gene-related peptide (CGRP) levels from baseline in both SHR and WKY (P<0.05), with no difference between 2 strains [21].
• In contrast, the sensitivity to methanandamide, which was not sensitive to antagonism by the combination of Caps and CB receptor antagonists, but has similar physicochemical properties to anandamide, did not vary between experiments [22].
• 5. Methanandamide and AM404 were less potent than AEA at activating VR1 [23].

Analytical, diagnostic and therapeutic context of LMFA08020040

• Since activation of cannabinoid CB1 receptors inhibits gastrointestinal transit in the mouse, this study analyzed the action of the cannabinoid receptor agonist methanandamide on distension-induced propulsive motility [12].
• After oral administration the duration of action of delta9-tetrahydrocannabinol, methanandamide and WIN 55212-2 is limited and decreased 4 h after administration [24].
• We used spontaneously active neuronal networks derived from dissociated embryonic murine spinal cord and auditory cortex and grown on substrate-integrated thin-film microelectrodes to determine characteristic responses to the cannabinoid agonists anandamide (AN) and methanandamide (MA) [25].

References