Figure 4.

Sites of action of agents associated with increased erectile function. Drugs may act through the peripheral or the central nervous system to achieve penile erection. Ascending and descending excitatory pathways responsible for penile erections rely on glutamate. Glutamate acts through N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors both in the brain and in the spinal cord. Descending neural input from brain inhibits erections mediated by serotonin (5-HT) and originates in the nucleus paragigantocellularis (nPGi). However, some serotonergic agents may facilitate erectile function. Trazodone acts in the periphery as a weak α-adrenergic-receptor antagonist and in the central nervous system as an α-adrenergic-receptor agonist at 5-HT_2C receptors via meta-chlorophenyl piperazine (mCPP). Agents that influence preganglionic neurons in the intermediolateral (IML) cell column of the sacral spinal cord influence erections. The paraventricular nucleus (PVN) in the brain is the site of action of oxytocin (OXY) and dopamine (D). Apomorphine and quinelorane act at D-receptors within the brain to help initiate penile erection. Melanocortins act at M3 receptors to influence penile erections, possibly by the actions of D or OXY. More rostral brain centers, such as the medial preoptic area (MPOA), influence the PVN as well as the nPGi regions. Yohimbine acts rostrally to the PVN at α₂-adrenal receptors to facilitate erections in some species.