IBMX (Synonyms: Isobutylmethylxanthine, 1-Methyl-3-Isobutylxanthine, NSC 165960, SC-2964)

IBMX is a non-specific inhibitor of phosphodiesterase (PDE) inhibitor that inhibits PDE3, PDE4 and PDE5 with IC50 values of 6.5, 26.3 and 31.7 µm, except PDE8A, PDE8B and PDE9[1,7].

In cardiac H9c2 cells,IBMX reduced loss of δψm caused by H(2)O(2), indicating that inhibition of PDEs can prevent the mPTP opening. However, IBMX could not inhibit the pore opening in cells transfected with the constitutively active GSK-3β (GSK-3β-S9A) mutant, suggesting a critical role of GSK-3β in the action of IBMX. IBMX also reduced reperfusion injury in a GSK-3β dependent manner[5]. Increasing cAMP-signaling with Forskolin or IBMX significantly facilitated neuronal functional maturation. A continuous application of IBMX to the differentiation medium substantially increased the functional expression of voltage-gated Na(+) and K(+) channels, as well as neuronal firing frequency[6].

Chronic exposure to cold caused pulmonary arterial hypertension and increased phosphodiesterase-1C (PDE-1C) expression in pulmonary arteries (PAs) in rats. After 8-week exposure to cold, Treatment with 8-IBMX significantly attenuated the cold-induced increase in right ventricular pressure. Cold exposure also caused right-ventricular hypertrophy, whereas 8-IBMX reversed cold-induced right ventricular hypertrophy. 8-IBMX abolished cold-induced upregulation of PDE-1C in PAs[4]. In hyperglycemic rat, all test compounds decreased blood glucose and the effect of milrinone was potentiated by glybenclamide. Milrinone or IBMX did not change plasma insulin levels, but it was augmented by combination of milrinone and glybenclamide. In both species, liver glycogen storage was decreased by IBMX, mc5, mc6 or MCPIP, increased by mc2 and was not changed in the presence of mc1[3]. ANG II increased ROMK channel activity in CCDs isolated from high-K (HK)-fed but not normal K (NK)-fed rats. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels[2].

References:
[1]: Wu BN, Lin RJ, et,al. KMUP-1, a xanthine derivative, induces relaxation of guinea-pig isolated trachea: the role of the epithelium, cyclic nucleotides and K+ channels. Br J Pharmacol. 2004 Aug;142(7):1105-14. doi: 10.1038/sj.bjp.0705791. Epub 2004 Jul 5. PMID: 15237094; PMCID: PMC1575170.
[2]: Wei Y, Liao Y,et,al. Angiotensin II type 2 receptor regulates ROMK-like K? channel activity in the renal cortical collecting duct during high dietary K? adaptation. Am J Physiol Renal Physiol. 2014 Oct 1;307(7):F833-43. doi: 10.1152/ajprenal.00141.2014. Epub 2014 Aug 6. PMID: 25100281; PMCID: PMC4187043.
[3]: Hosseini A, Shafiee-Nick R, et,al. Differential metabolic effects of novel cilostamide analogs, methyl carbostiryl derivatives, on mouse and hyperglycemic rat. Iran J Basic Med Sci. 2012 Jul;15(4):916-25. PMID: 23493150; PMCID: PMC3586914.
[4]: Crosswhite P, Sun Z. Inhibition of phosphodiesterase-1 attenuates cold-induced pulmonary hypertension. Hypertension. 2013 Mar;61(3):585-92. doi: 10.1161/HYPERTENSIONAHA.111.00676. Epub 2013 Jan 14. PMID: 23319544; PMCID: PMC4050371.
[5]: Chanoit G, Zhou J,et,al. Inhibition of phosphodiesterases leads to prevention of the mitochondrial permeability transition pore opening and reperfusion injury in cardiac H9c2 cells. Cardiovasc Drugs Ther. 2011 Aug;25(4):299-306. doi: 10.1007/s10557-011-6310-z. PMID: 21643720.
[6]: Lepski G, Jannes CE, et,al. cAMP promotes the differentiation of neural progenitor cells in vitro via modulation of voltage-gated calcium channels. Front Cell Neurosci. 2013 Sep 19;7:155. doi: 10.3389/fncel.2013.00155. PMID: 24065885; PMCID: PMC3777016.
[7]: Soderling SH, Bayuga SJ, et,al. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem. 1998 Jun 19;273(25):15553-8. doi: 10.1074/jbc.273.25.15553. PMID: 9624145.