Comparison of the visceral antinociceptive effects of spinally administered MPV-2426 (fadolmidine) and clonidine in the rat.

Abstract

BACKGROUND:

The authors determined the visceral antinociceptive effect induced by MPV-2426 (fadolmidine), a selective alpha 2 -adrenoceptor agonist, in rats with and without inflammation of the colon. They also determined whether the sympathetic nervous system or intact descending pathways are critical for the alpha 2 -adrenoceptor-induced visceral antinociception.

METHODS:

Spinal neuronal responses evoked by colorectal distension were recorded in pentobarbitone-anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was used as a reference alpha 2 -adrenoceptor agonist. Inflammation of the colon was induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A midthoracic transection of the spinal cord was performed to study the role of descending pathways.

RESULTS:

Spinal administration of MPV-2426 produced a dose-dependent attenuation of responses evoked by colorectal distension, and this effect was of the same percentual magnitude in inflamed as in noninflamed animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy but not influenced by spinal transection.

CONCLUSIONS:

Spinally administered MPV-2426 produces a dose-dependent visceral antinociception as well in animals with an inflammation of the colon as in controls. The visceral antinociceptive effect induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact sympathetic nervous system or intact brainstem-spinal pathway is not critical for the MPV-2426-induced visceral antinociception.

• Authors: Antti Pertovaara, Jaakko Kalmari
• Journal: Anesthesiology (Anesthesiology) Vol. 98 Issue 1 Pg. 189-94 (Jan 2003) ISSN: 0003-3022 [Print] United States
• PMID: 12502996 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Analgesics
• Imidazoles
• Indans
• Receptors, Adrenergic, alpha-2
• Clonidine
• radolmidine

Topics

• Adrenergic alpha-Agonists (administration & dosage, pharmacology)
• Analgesics (administration & dosage, pharmacology)
• Anesthesia
• Animals
• Clonidine (administration & dosage, pharmacology)
• Colitis (physiopathology)
• Colon (physiology)
• Dose-Response Relationship, Drug
• Hyperalgesia (drug therapy)
• Imidazoles (administration & dosage, pharmacology)
• Indans (administration & dosage, pharmacology)
• Injections, Spinal
• Male
• Pain Measurement (drug effects)
• Physical Stimulation
• Posterior Horn Cells (drug effects)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, alpha-2 (administration & dosage)
• Rectum (physiology)
• Sympathectomy, Chemical