Interactions of prazosin with non-steroidal anti-inflammatory drugs

The non-steroidal anti-inflammatory drugs (NSAIDs) are used in the treatment of a variety of pain and inflammatory conditions, mainly because its molecular target is the inhibition of the enzyme cyclooxygenase (COX). Experimental studies suggest that inhibition of COX does not fully explain the antinociceptive effect of these drugs. The aim of the present study was to determine, using as a noxious chemical stimulus the acetic acid algesiometric test, the modulatory interactions between the antinociceptive effect of some NSAIDs and the selective α₁-adrenergic receptor antagonist prazosin (PRA), at spinal and supraspinal levels. The simultaneous intraperitoneal administration of NSAIDs with PRA, analyzed by isobolograms, produced supra-additive interactions; however, when the drugs were administered intrathecally, the interactions were only additive, with the exception of thode of naproxen and paracetamol, which were supra-additive. The coadministration of PRA and NSAIDs, either systemically or intrathecally, never resulted in sub-additive or antagonistic effects upon the antinociceptive activity elicited by NSAIDs. The results of the present work suggest that the antinociception induced by NSAIDs involves some form of interaction with spinal and supraspinal α₁-adrenergic receptors, which appears to be dearly additive or supra-additive.