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Psoriatic epidermis shows excessive cell proliferation, incomplete morphogenesis, and glycogen accumulation. These three features may result from coordinate misregulation by the previously reported abnormal lesional ratio of cyclic AMP/cyclic GMP. If so, it is possible that psoriasis might improve by topical application of an agent known to alter cellular levels of cyclic nucleotides. In the present study papaverine (3.0 × 10-4 M) produced a 210% increase (.02 < p < .05) in epidermal cyclic AMP levels in vitro. Therefore, 1% papaverine cream (approximately 2.7 × 10-2 M papaverine) was chosen to establish whether a cyclic AMP elevating agent could improve a psoriatic lesion. A double-blind comparison of 1% papaverine cream versus cream alone was conducted on matched lesions in 45 patients. Of those patients showing differential improvement (i.e., only one lesion of the pair improved), 81% (p = 0.011) of those showing a response in the center of the lesion and 77% (p = 0.046) of these improving at the edge had applied papaverine. Although no attempts were made to develop a papaverine formulation with immediate therapeutic utility, the numerically significant papaverine results suggest future therapeutic developments. [ABSTRACT FROM AUTHOR]