Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy.
We have recently demonstrated that serotonin (5-HT) increases the production of type 4 collagen by cultured human mesangial cells. Here we examined the clinical effects of a 5-HT(A2) receptor antagonist whether it would prevent the development or progression of diabetic nephropathy. We compared the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We then investigated the effects of 24-month treatment with sarpogrelate hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10 type 2 diabetics with microalbuminuria, compared with not treated control group. Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day) than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g Cr, P<0.05), which was persistently seen during the treatment, while no such change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate that high levels of 5-HT in type 2 diabetics may be one of the underlying mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor antagonists may reduce or inhibit the development of nephropathy.
Takahashi
Takeshi
T
Department of Internal Medicine, Kumamoto National Hospital Diabetes Center, 1-5 Ninomaru, Kumamoto City, Kumamoto 860-0008, Japan. t99@zk9.so-net.ne.jp
Yano
Miyuki
M
Minami
Junko
J
Haraguchi
Tomoko
T
Koga
Naoko
N
Higashi
Kiichiro
K
Kobori
Shozo
S
D000419:Albuminuria / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000517:prevention & control* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012044:Regression Analysis; D012701:Serotonin / Q000652:urine; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013386:Succinates / Q000627:therapeutic use*; D013997:Time Factors
D006442:Glycated Hemoglobin; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate