Binodenoson

RN104, named 2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole, is a thiazolyl hydrazone derivative with promising antifungal activity. Pharmacokinetic profile of the RN104 was evaluated in mice plasma using a developed and validated bioanalytical method by LC-MS/MS. Clotrimazole was used as internal standard. The analytes were extracted by a protein precipitation procedure and separated on a C18 end-capped column and mobile phase composed of acetonitrile - 0.1% formic acid (85:15, v/v), in isocratic mode. Electrospray ionization in positive ionization mode (ESI + ) and multiple reaction monitoring (MRM) were employed using the transitions m/z 286.1 → m/z 176.1 (quantifier) and m/z 286.1 → m/z 112.2 (qualifier) for RN104 and m/z 345.2 → m/z 277.1 (quantifier) and m/z 345.2 → m/z 165.2 (qualifier) for internal standard. The method was validated and proved to be linear, accurate, precise, and selective over the range 0.625 to 40.0 ng/mL. The pharmacokinetic model that best fit the data was the bicompartmental model. The maximum plasmatic concentration was reached 20 min after administration (per os and intraperitoneal) and the highest plasma concentration of RN104 was found after per os administration at a dosage of 50 mg/kg compared to i.p. administration at 10 mg/kg.

Selective adenosine receptor agonists have several advantages for use as stress agents in conjunction with myocardial perfusion imaging compared to the non selective agents such as adenosine and dipyridamole. This review will summarize the pre-clinical and clinical data on the selective adenosine agonist stress agents regadenoson (Lexiscan(®)), binodenoson (CorVue™) and apadenoson (Stedivaze™) that have been studied so far with focus on regadenoson that has the most clinical data published so far. The article will review the adenosine receptor types and properties. It will also review the various attributes of the selective adenosine agonists including their pharmacology, pharmacokinetics and pharmacodynamics, their coronary vasodilatory and hemodynamic effects, their safety and side effects, their interactions with other drugs and their use with myocardial perfusion imaging. The landmark trials of the selective adenosine agonists will be reviewed as well as their use in special patient populations undergoing stress myocardial perfusion imaging.