(The FASEB Journal. 2007;21:875.2)
© 2007 FASEB
Pharmacological studies of AGI-1140 in a rat model of erectile dysfunction
Tamer Aboushwareb,
Karl-Erik Andersson and
George J. Christ
Wake Forest University, Wake Forest Institute for Regenerative Medicine and Department of Physiology & Pharmacology, Medical Center Boulevard, Winston-Salem, NC, 27157
ABSTRACT
Although sildenafil (SIL; Viagra) has revolutionized the treatment of erectile dysfunction, it is not effective in all patient populations and untoward side effects are common. Since there is room for improved therapy, the goal of these studies was to evaluate the potential of a novel compound, the bicyclic monoterpene diol AGI-1140, believed to act through the NO/cGMP/PKG signalling pathway, in a rat model of age-related erectile dysfunction. To this end, we examined the impact of a proprietary compound (AGI-1140; AGI Dermatics) on the cavernous nerve stimulated intracavernous pressure (ICP) response on 40 male retired breeder rats (
600 g body weight). Submaximal control ICP responses were obtained (1–4 mA current stimulation) prior to administration of either AGI=1140 (0.3 or 1 mg/kg) or SIL (1.0 mg/kg). Drugs were given by either the subcutaneous (sc) or intravenous (iv) routes. 30 and 60 minutes later, the same submaximal stimulation was reapplied. AGI-1140 produced a significant increase in the erectile response at 1 mg/kg via the subcutaneous (sc) route, with results comparable to same dose of sildenafil given iv and superior to 1 mg/kg SIL sc. AGI-1140 had no effect when given via the iv route. Thus, AGI-1140 administered sc at a dose of 1 mg/kg had similar efficacy to that of sildenafil 1 mg/kg administered iv. Further studies are needed to clarify the exact mode of action of AGI-1140 and to detect any side effects.
