Anti-parkinsonian agents procyclidine and ethopropazine alleviate thermal hyperalgesia in neuropathic rats.

Abstract

Procyclidine and ethopropazine, widely used as anti-parkinsonian agents because of their anti-cholinergic action, are also known to have NMDA antagonist properties. Unlike other NMDA antagonists, these agents-because of their anti-cholinergic action-are devoid of neurotoxic side effects. In the present study, we used a sciatic nerve ligation model that produces a hyperalgesic (neuropathic pain) state in adult rats to evaluate the ability of procyclidine or ethopropazine, either alone or in combination with an alpha(2) adrenergic agonist, to ameliorate neuropathic pain. We found that both procyclidine and ethopropazine alleviated thermal hyperalgesia in a dose dependent manner; when a marginally effective dose of these agents was combined with an ineffective dose of an alpha(2) adrenergic agonist (clonidine or guanabenz), the combination therapy provided effective and long-lasting relief from neuropathic pain. In addition, the combination therapy was free from neurotoxic or behavioral side effects, and hyperactivity, a side effect associated with procyclidine monotherapy, was counteracted by clonidine.

• Authors: V Jevtovic-Todorovic, A P Meyenburg, J W Olney, D F Wozniak
• Journal: Neuropharmacology (Neuropharmacology) Vol. 44 Issue 6 Pg. 739-48 (May 2003) ISSN: 0028-3908 [Print] England
• PMID: 12681372 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic alpha-Agonists
• Antiparkinson Agents
• Phenothiazines
• Receptors, Adrenergic, alpha-2
• Receptors, N-Methyl-D-Aspartate
• profenamine
• Procyclidine
• Guanabenz
• Clonidine

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Animals
• Antiparkinson Agents (pharmacology)
• Clonidine (pharmacology)
• Constriction, Pathologic (complications)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Guanabenz (pharmacology)
• Hyperalgesia (drug therapy, etiology, physiopathology)
• Ligation
• Pain Measurement
• Peripheral Nervous System Diseases (drug therapy, etiology, physiopathology)
• Phenothiazines (therapeutic use)
• Procyclidine (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, alpha-2 (drug effects)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Sciatic Nerve