We know that sildenafil (Viagra) helps restore erectile functioning, but not many people know that it also has cognitive-enhancing and neuroprotective effects in rodents. A double-blind, placebo-controlled study from Iran by Akhondzadeh et al suggests that sildenafil can significantly improve negative symptoms of schizophrenia. The study may lead to an important adjunctive use of this drug if it is replicated with a larger sample. The putative mechanism is the inhibition of phosphodiesterase 5 (PDE5), resulting in increased cyclic guanosine monophosphate (cGMP), which may correct the hypofunctioning N-methyl-D-aspartic acid (NMDA) glutamate receptor believed to be associated with elevated dopamine in the mesolimbic tract (causing positive symptoms) and a decline in dopamine in the mesocortical tract (causing cognitive deficits and negative symptoms).
Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial
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