Phosphodiesterases (PDE) enzymatically convert the cyclic nucleotide second messengers cAMP and cGMP to 5’-AMP and 5’-GMP, respectively, thus terminating signal transduction. The cAMP-specific PDE4 isoforms may be particularly important in certain respiratory and neurological diseases.1,2 CP 80633 is a selective inhibitor of PDE4 (IC50 = 1.27 μM for PDE4 versus. >100 μM for PDE1, PDE2, PDE3, and PDE5).3 It potentiates PGE1-dependent increases in cAMP levels in eosinophils, monocytes, and T-cells, inhibits eosinophil superoxide production (IC50 < 0.6 μM), and blocks LPS-induced TNF-α release from monocytes (IC50 = 0.22 μM).3 CP 80633 (1 mg/kg) significantly reduces antigen-induced airway inflammation in atopic guinea pigs, monkeys, and mice.4,5
1
Spina, D. PDE4 inhibitors: Current status. Br J Pharmacol155308-315(2008).
2
O'Donnell, J.M., and Zhang, H. Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). Trends Pharmacol Sci25(3)158-163(2004).
3
Cohan, V.L., Showell, H.J., Fisher, D.A., et al. In vitro pharmacology of the novel phosphodiesterase type 4 inhibitor, CP-80633. J Pharmacol Exp Ther278(3)1356-1361(1996).
4
Turner, C.R., Cohan, V.L., Cheng, J.B., et al. The in vivo pharmacology of CP-80, 633, a selective inhibitor of phosphodiesterase 4. J Pharmacol Exp Ther278(3)1349-1355(1996).
5
Cheng, J.B., Watson, J.W., Pazoles, C.J., et al. The phosphodiesterase type 4 (PDE4) inhibitor CP-80,633 elevates plasma cyclic AMP levels and decreases tumor necrosis factor-α (TNFα) production in mice: Effect of adrenalectomy. J Pharmacol Exp Ther280621-626(1997).
O'Donnell, J.M., and Zhang, H. Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). Trends Pharmacol Sci25(3)158-163(2004).
Cheng, J.B., Watson, J.W., Pazoles, C.J., et al. The phosphodiesterase type 4 (PDE4) inhibitor CP-80,633 elevates plasma cyclic AMP levels and decreases tumor necrosis factor-α (TNFα) production in mice: Effect of adrenalectomy. J Pharmacol Exp Ther280621-626(1997).
Cohan, V.L., Showell, H.J., Fisher, D.A., et al. In vitro pharmacology of the novel phosphodiesterase type 4 inhibitor, CP-80633. J Pharmacol Exp Ther278(3)1356-1361(1996).
Spina, D. PDE4 inhibitors: Current status. Br J Pharmacol155308-315(2008).
Turner, C.R., Cohan, V.L., Cheng, J.B., et al. The in vivo pharmacology of CP-80, 633, a selective inhibitor of phosphodiesterase 4. J Pharmacol Exp Ther278(3)1349-1355(1996).