Disease relevance of Mdl 12330A

• Inhibition of the adenylate cyclase by N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride (MDL 12330A; 20-1,000 microM) under zero-Ca2+ conditions irreversibly inhibited the cyclic AMP increase produced by hypoxia [1].
• An adenylate cyclase inhibitor, RMI 12330A, is able to depress cAMP synthesis stimulated by serotonin in the abdominal ganglion of Aplysia depilans and punctata [2].
• The VIP antagonist, PG-97-269, and the adenylate cyclase inhibitor, MDL-12330A, but not SQ-22536 or pertussis toxin, blocked the cAMP responses to these peptides [3].

High impact information on Mdl 12330A

• To investigate this problem we used two drugs that prevent intestinal secretion in vitro, RMI 12330A (Richardson Merrell), and the antipsychotic pheno-thiazine trifluoperazine (Stelazine, Smith, Kline and French) [4].
• An inhibitor of mammalian adenylate cyclase, MDL-12330A, was tested in combination with azoles; a synergistic effect was observed against azole-susceptible and -resistant strains of C. albicans and five of six non-C. albicans Candida species [5].
• In thymocyte plasma membrane preparations, MDL 12330A induced a concentration-dependent inhibition of both basal enzyme activity (activity in the absence of hormone) and the increase in activity induced by T3 and epinephrine [6].
• 4 RMI 12330A uncoupled mitochondrial oxidative phosphorylation; the classical uncoupler, dinitrophenol, had the same effects on cardiac dynamics as RMI 12330A [7].
• 2 In the isolated work-performing heart of the guinea-pig, RMI 12330A (IC50 of 1.1 X 10(-6) M) depressed all cardiac functions: pressures developed, dP/dt, contractile force, dF/dt, work performance and stroke work [7].

Biological context of Mdl 12330A

• Furthermore, intrauterine injection of RMI-12330 A (50 microgram or 500 microgram/uterine horn), an inhibitor of adenylyl cyclases, on day 5 of pregnancy interrupted embryo development and implantation of the embryo [8].

Anatomical context of Mdl 12330A

• The effect of trifluoperazine and RMI 12330A on D-Galactose accumulation was studied in isolated rat intestinal mucosa [9].

Associations of Mdl 12330A with other chemical compounds

• The stimulation of cAMP by GLP-1 and forskolin was effectively inhibited by the adenylate cyclase inhibitors MDL-12330A and SQ-22536, confirming that the increased cAMP is through the AC pathway [10].
• The adenylyl cyclase inhibitor, MDL 12330A, blocked the effect of GHRH and GHRP-2 on intracellular cAMP levels, whereas the Ca2+ channel blocker Co2+ (0.5 mM) did not attenuate the cAMP response [11].
• The effect of Bay K 8644 was antagonized by the adenylyl cyclase inhibitor MDL 12330A, suggesting a link between Ca(2+) influx, cAMP formation, and AANAT activity in retinal cells [12].
• Inhibition of ADP-ribosyltransferase activity of cholera toxin by MDL 12330A and chlorpromazine [13].
• Moreover, the adenylate cyclase inhibitor, MDL-12330A, significantly reduced ACh-induced luminescence [14].

Gene context of Mdl 12330A

• RMI 12330A, an inhibitor of cyclic nucleotide phosphodiesterases and adenylate cyclase in kidney preparations [15].

References