Chronic exposure to Ro20-1724 protects dopaminergic neurons in vitro against the neurotoxic action of N-methyl-D-aspartate and 1-methyl-4-phenylpyridinium.

Using organotypic cultures of rat ventral mesencephalon, the effects of chronic (12-15 day) exposure to the type IV cAMP phosphodiesterase inhibitor, Ro20-1724, were examined. At concentrations of 10(-8)-10(-5) M, Ro20-1724 alone had no effect upon the number of tyrosine hydroxylase-positive neurons or upon neurite outgrowth. However, the drug offered significant protection, with maximum effect at 10(-6) M, against subsequent acute (48 h) exposure to the neurotoxic agents 1-methyl-4-phenylpyridinium (MPP+) and N-methyl-D-aspartate (NMDA).