Journal Article

Effects of risperidone on amino acid metabolism, glucose, and kidney function in healthy adults: A pilot randomized controlled trial

Nishioka, Ryo, Miyagi, Sakae, Tamai, Akira, Nakade, Yusuke, Sako, Keisuke, Tsuge, Shunsuke, Tsubomoto, Makoto, Mizushima, Ichiro, Miyagawa, Taro, Kikuchi, Mitsuru, Oshima, Megumi, Toyama, Tadashi, Ogura, Hisayuki, Koshino, Akihiko, Mita, Masashi, Hara, Akinori, Yuasa, Takahiro, Kinoshita, Masashi, Horikoshi, Keisuke, Shimizu, Miho, Tokumaru, Toshiaki, Ito, Kiyoaki, Nakada, Mitsutoshi, Minami, Taichiro, Wada, Takashi, Nakagawa, Shiori, Iwata, Yasunori, Kitajima, Shinji, Sakai, Norihiko

2025

Overview

d-serine administration prevents kidney damage in murine models of acute kidney injury, and risperidone inhibits the activity of d-amino acid oxidase, which regulate plasma d-amino acid levels. This pilot randomized controlled trial investigated the effects of risperidone on glucose, amino acid metabolism, and kidney function in healthy adults. Healthy adults with a homeostasis model assessment of insulin resistance (HOMA-IR) of ≥ 1.6 and estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73m2 were randomly assigned to the risperidone and control groups. The risperidone group received 0.5 mg/day risperidone for 4 days. The primary outcome was mean change in HOMA-IR on day 5, and the secondary outcomes were changes in d-amino acid levels, eGFR, and urinary albumin. Seven participants were randomized to the risperidone and control groups. The changes in HOMA-IR, eGFR, and urinary albumin on day 5 were not significantly different between the two groups (all p > 0.05). Mean changes in plasma d-serine level and urinary d-serine/creatinine ratio were significantly higher in the risperidone group than in the control group (0.2 vs. -0.3 nmol/mL, p = 0.03 and 38.2 vs. -25.8 nmol/mL, p = 0.01, respectively). Short-term risperidone affects d-serine metabolism without instigating acute adverse effects on kidney or glucose homeostasis in healthy individuals. Clinical Trial Registry number: This study was registered with the Japan Registry for Clinical Trials (jRCTs041210165).

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Adults / Albumin / Albumins / Amino acid metabolism / Amino acid oxidase / Amino acid sequence / Amino acids / Amino Acids - blood / Amino Acids - metabolism / Animal models / Antipsychotics / Blood Glucose - drug effects / Blood Glucose - metabolism / Clinical trials / Creatinine / D-Amino-acid oxidase / D-Serine / Damage prevention / Epidermal growth factor receptors / Female / Glomerular filtration rate / Glomerular Filtration Rate - drug effects / Glucose / Glucose - metabolism / Gut microbiota / Health aspects / Healthy Volunteers / Hemoglobin / Homeostasis / Humans / Injury prevention / Insulin Resistance / Kidney - drug effects / Kidney - metabolism / Kidney - physiology / Kidney diseases / Kidney Function Tests / Kidneys / Laboratories / Male / Metabolism / Middle Aged / Peptides / Pilot Projects / Psychotropic drugs / Risperidone / Risperidone - administration & dosage / Risperidone - adverse effects / Risperidone - pharmacology / Schizophrenia / Serine - blood / Serine - urine / Testing / Urine / Young Adult