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Pramlintide’s effects upon administration to patients almostcertainly arise in significant measure from directAMY-mediated actions within the brainstem. Amylin receptorsare abundant in the circumventricular organs, includingthe subfornical organ (where AMY1(a) receptors areknown to be expressed in relative abundance), the organumvasculosum lateralis terminalis, and the area postrema(AMY3(a)), where the action of pramlintide (or of -cell–secretedamylin) is not precluded by a diffusional BBB.Amylin receptors are also expressed in various other brainareas, in particular the nucleus accumbens, but neitheramylin or pramlintide circulating in the bloodstream arelikely to exert any action at these BBB-shielded locations.Direct amylin receptor–mediated actions of pramlintide in the periphery, if any, remain poorly characterized.Unsurprisingly, though, the appetite-suppressing actions,and benefits of pramlintide and amylin agonists in general,are receiving significant clinical and scientific attention.