The NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has antinociceptive effect after intrathecal injection in the rat

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Abstract

This behavioral study was performed in order to delineate the antinociceptive effects of and the influence on motor function of a highly potent, competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4yl) propyl-1-phosphonic acid (CPP). After intrathecal (i.t.) administration of CPP to chronically catheterized rats, antinociception was studied in 3 different nociceptive tests: the tail-flick test, the hot-plate test, and the formalin test.

The lowest dose producing visible motor dysfunction was 1 nmol, with 2 of 8 animals showing slight ataxia. Dose-related motor dysfunction and apparent sedation was present after 5 and 10 nmol. Dose-related antinociception was evident in the thermal tests following doses that produced little or no motor dysfunction. In the tail-flick test, the antinociceptive effect was attenuated at higher doses, resulting in a bell-shaped dose-response relationship. Dose-related antinociception was found in both the first and second phase of the formalin test following doses from 0.25 up to 1 nmol.

The present study shows that the competitive NMDA antagonist CPP has an antinociceptive effect in doses that do not affect motor function. Furthermore, antinociception was evident in both phasic and tonic nociceptive tests. Finally, the dose-response relationship in the tail-flick test was bell-shaped. As discussed this indicates that NMDA receptors may be involved in functionally divergent nociceptive systems.

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