A role for spinal, but not supraspinal, alpha sub(2) adrenergic receptors in the actions of improgan, a powerful, non-opioid analgesic

• Published in: Brain research Vol. 923; no. 1-2; pp. 12 - 19
• Main Authors: Svokos, K, Nalwalk, J W, Leurs, R, Menge, WMPB, Timmerman, H, Hough, L B
• Format: Journal Article
• Language: English
• Published: 27.12.2001
• Subjects: improgan; yohimbine
• ISSN: 0006-8993

Improgan is a derivative of cimetidine that induces non-opioid antinociception after intracerebroventricular (i.c.v.) administration, but the mechanism of action of this compound remains unknown. Since activation of either supraspinal or spinal alpha sub(2) adrenergic receptors can induce antinociception, and since improgan showed affinity for these receptors in vitro, the effects of the alpha sub(2) antagonist yohimbine on improgan antinociception were presently studied in rats on the hot plate and tail flick tests. Systemic yohimbine pretreatment (4 mg/kg, i.p.) completely blocked improgan antinociception (80 mu g, i.c.v.), suggesting a mediator role for alpha sub(2) receptors. However, i.c.v. pretreatment with yohimbine (30 mu g) had no effect on improgan antinociception. Since this treatment completely antagonized clonidine antinociception (40 mu g, i.c.v.), supraspinal alpha sub(2) receptors seem to mediate the antinociceptive effects of clonidine, but not that produced by improgan. In contrast, intrathecal (i.t.) yohimbine pretreatment (30 mu g) completely blocked the antinociception elicited by i.c.v. improgan and i.c.v. morphine. These results suggest that spinal (but not supraspinal) alpha sub(2) adrenergic receptors play a significant role in the pain-relieving actions of improgan. Furthermore, although improgan shows some affinity at alpha sub(2) receptors, this drug does not act directly at these receptors to induce antinociceptive responses. Like several other classes of analgesics, improgan-like drugs seem to activate non-opioid, descending pain-relieving circuits.