TITLE:
Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs
AUTHORS:
Jun Kawahara, Rio Uno, Honami Kojima, Miyako Yoshida, Takahiro Uchida, Hidekazu Ikezaki, Masaaki Habara
KEYWORDS:
Adenylic Acid, Bitterness, Antipsychotic Medicine, Amitriptyline, Chlorpromazine, Haloperidol, Risperidone, Taste Sensor, Drug-Drug Interaction
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.13 No.10,
October
31,
2022
ABSTRACT: The purpose of the present study was to examine the effect of adenylic acid (adenosine 5-monophosphate; AMP), a known nutritional enhancer, on inhibiting the bitterness of antipsychotic medicines administered to patients with mental illnesses, including children. First, we chose four antipsychotic medicines, amitriptyline hydrochloride (AMT), chlorpromazine hydrochloride (CPZ), haloperidol (HPD) and risperidone (RIS) and evaluated the inhibition of their bitterness by AMP through taste sensor measurements. AMP showed a significant bitterness inhibition effect on all drugs. Second, MarvinSketch analysis revealed the potential formation of electrostatic interactions between ionic forms (IV) of AMP and ionic (cationic) forms of each drug, which resulted in bitterness suppression. Third, chemical shift perturbations in 1H-NMR studies suggested an interaction between the phosphate group of AMP and amino group of AMT, CPZ, HPD and RIS. Last, conventional elution experiments of up to 1 min simulating oral cavity conditions were performed for 1 whole AMT tablet, half AMT tablet, crushed half AMT tablet, and crushed AMT tablet containing AMP powder/solution (1, 3 mM potency). The taste sensor output values of the crushed AMT tablet containing AMP powder/solution (1, 3 mM potency) were significantly lower than those of the crushed tablet.