Neurologic, Psychological, and Aggressive Disturbances with Sildenafil
Abstract
BACKGROUND: Anecdotal reports and case studies have described psychological disturbances and aggressive behavior in some men taking sildenafil. In the course of assisting the defense in a trial in which a man was alleged to have committed rape and in which sildenafil was implicated, a mechanistic hypothesis was formulated by the first author for central nervous system (CNS) adverse effects associated with the use of sildenafil. OBJECTIVE: To examine whether there was any scientific information available to suggest a possible mechanism for or an association between exposure to sildenafil and aggressive behavior. METHODS: The scientific literature on sildenafil, nitric oxide (NO), and the NO-cyclic-guanosine monophosphate (cyclic-GMP) signaling pathway was reviewed. Adverse event reports that referenced sildenafil and were filed with the Food and Drug Administration Adverse Event Reporting System between January 4, 1998, and February 21, 2001, also were examined. RESULTS: Published studies reported that sildenafil crosses the blood-brain barrier, that it exerts various biochemical and physiologic effects in the brain, and that it affects information processing. Other published reports indicated that phosphodiesterase type 5 (PDE-5), NO synthase, and guanylyl cyclase are present at highest activities in areas of the brain responsible for behavior, sexual drive, and emotion, and that NO modulates aggression and sexual behavior in male mice. In addition, 274 adverse event reports…
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