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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects*; D020889:Rolipram; D013116:Spinal Cord / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D010643:Phenoxybenzamine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003533:Cyproheptadine; D013806:Theophylline; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine