The stimulatory action of phosphodiesterase inhibitors on the flexor reflex of the hind limb in the spinal rat.

We studied the action of the following phosphodiesterase inhibitors (PDEIs): rolipram (4-[3-cyclopentoxy-5-methoxyphenyl]-2-pyrrolidione), Ro 20-1724 (4-[3-butoxy-4-methoxybenzyl]-2-imidazolidione), 1-methyl-3-isobutylxanthine (IMBX) and theophylline on flexor reflex activity of the hind limb in the spinal rat. Potentiation of this reflex is thought to be due to enhancement of either 5-hydroxytryptaminergic or alpha-adrenergic transmission in the spinal cord. All the inhibitors potentiated flexor reflex activity in a dose-dependent manner in the following order of potency: rolipram greater than Ro 20-1724 greater than IBMX greater than theophylline. Their stimulatory action in this model paralleled their known potency in inhibiting phosphodiesterase (PDE). Neither the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine nor the alpha-adrenoceptor blocker phenoxybenzamine prevented potentiation of flexor reflex activity by PDEIs. It is suggested that (1) the PDEIs potentiate flexor reflex activity through a novel spinal mechanism which does not involve alpha-adrenoceptors of 5-HT receptors in the spinal cord but rather is related to the inhibition of PDE localized postsynaptically; (2) flexor reflex activity in the spinal rat can be a useful experimental preparation to estimate the in vivo effects of known PDEIs.