Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs  

作　　者：Jun Kawahara Rio Uno Honami Kojima Miyako Yoshida Takahiro Uchida Hidekazu Ikezaki Masaaki Habara Jun Kawahara;Rio Uno;Honami Kojima;Miyako Yoshida;Takahiro Uchida;Hidekazu Ikezaki;Masaaki Habara(Faculty of Pharmaceutical Science, Mukogawa Women’s University, Nishinomiya, Hyogo, Japan;Intelligent Sensor Technology Inc., Atsugi, Kanagawa, Japan)

机构地区：[1]Faculty of Pharmaceutical Science, Mukogawa Women’s University, Nishinomiya, Hyogo, Japan [2]Intelligent Sensor Technology Inc., Atsugi, Kanagawa, Japan

出　　处：《Pharmacology & Pharmacy》2022年第10期429-446,共18页药理与制药（英文）

摘　　要：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.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.

关 键 词：Adenylic Acid BITTERNESS Antipsychotic Medicine AMITRIPTYLINE CHLORPROMAZINE HALOPERIDOL RISPERIDONE Taste Sensor Drug-Drug Interaction 

分 类 号：U46[机械工程—车辆工程]