Meariman JK, Sutphen JC, Gao J, et al. - Nalfurafine, a G-protein–biased kappa opioid receptor agonist, enhances the diuresis to standard-of-care diuretics without resulting in an excessive loss of electrolytes.

• This study involved Sprague-Dawley rats treated with an intravenous bolus of nalfurafine, a diuretic, or a combination, to assess the cardiovascular and renal responses to intravenous and oral nalfurafine alone and in combination with furosemide, hydrochlorothiazide, or amiloride.

• A marked diuresis, antinatriuresis, antikaliuresis, and a reduction in mean arterial pressure were brought about by intravenous and oral nalfurafine.

• Relative to diuretic alone, intravenous coadministration with nalfurafine significantly raised urine output to furosemide and hydrochlorothiazide and reduced sodium and potassium excretion.

• Nalfurafine/diuretic combination therapy induced decrease in mean arterial pressure than diuretics alone.

• Oral coadministration of nalfurafine significantly elevated urine output to hydrochlorothiazide and reduced sodium and potassium excretion, whereas together with furosemide merely limited the amount of sodium excreted.

• Both intravenous and oral coadministration of nalfurafine resulted in improved diuresis to amiloride and reduced sodium excretion.