Disease relevance of AM-356

• Furthermore, experiments with mice have demonstrated that (R)-methanandamide also possesses cannabimimetric properties in vivo, as established by the four tests of hypothermia, hypokinesia, ring immobility, and antinociception [1].
• Moreover, methAEA-induced potentiation of BK channel currents was not affected by pretreatment with a CB1 antagonist (AM251), modulators of G proteins (cholera and pertussis toxins) or by application of a selective CB2 agonist (JWH133) [2].

High impact information on AM-356

• 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) [3].
• The thio analogs of both anandamide and (R)-methanandamide showed very weak affinity for CB1 [4].
• Of the analogs tested, (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide [(R)-methanandamide] exhibited the highest affinity for the cannabinoid receptor with a Ki of 20 +/- 1.6 nM, 4-fold lower than that of anandamide (Ki = 78 +/- 2 nM) [1].
• Under cell-attached patch-clamp conditions, application of methAEA to the bathing solution increased BK channel activity; however, methAEA did not alter channel activity in the excised inside-out patch mode even when ATP was present on the cytoplasmic side of the membrane [2].
• Enhancement of androgen receptor expression induced by (R)-methanandamide in prostate LNCaP cells [5].

Biological context of AM-356

• AM-356 elicited biphasic effects on the incidence of hyperactivated sperm motility (HA) between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM) it stimulated HA [6].

Anatomical context of AM-356

• Application of methAEA to mouse aortic myocytes significantly increased BK channel currents [2].
• (R)-methanandamide inhibits receptor-induced calcium responses by depleting internal calcium stores in cultured astrocytes [7].

Associations of AM-356 with other chemical compounds

• OBJECTIVE: Here we examine antagonism where the cannabinoid CB1 receptor agonist [Delta(9)-THC and (R)-methanandamide] dose is held constant (i.e., the training dose) and the antagonist {i.e., SR-141716 and AM-251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 2 ml/kg]} dose varied [8].

Gene context of AM-356

• (R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide [9].

Analytical, diagnostic and therapeutic context of AM-356

• Denervation of the infused kidney blocked the MethA-induced increases in urine flow rate bilaterally without altering MethA-induced decreases in MAP [3].
• Western immunoassays performed using three opioid receptor antibodies, a cannabinoid CB(1) receptor antibody and a transient receptor potential vanilloid type 1(TRPV(1)) receptor antibody, yielded no change in receptor protein levels after short-term arvanil, (R)-methanandamide or Delta(9)-THC administration [10].
• There was a dose-related suppression of ambulation (horizontal activity) and rearing (vertical activity) after (R)-methanandamide administration [11].

References