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

• Published in: Neuropharmacology 2003-05, Vol.44 (6), p.739-748
• Main Authors: Jevtovic-Todorovic, V, Meyenburg, A.P, Olney, J.W, Wozniak, D.F
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Alpha-2 agonists; Animals; Antiparkinson Agents - pharmacology; Biological and medical sciences; Clonidine; Clonidine - pharmacology; Constriction, Pathologic - complications; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Guanabenz; Guanabenz - pharmacology; Hyperalgesia - drug therapy; Hyperalgesia - etiology; Hyperalgesia - physiopathology; Ligation; Medical sciences; Neurotoxicity; NMDA antagonists; Pain Measurement; Paw thermal stimulation; Peripheral Nervous System Diseases - drug therapy; Peripheral Nervous System Diseases - etiology; Peripheral Nervous System Diseases - 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
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(03)00069-8

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 α 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 α 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.