Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces albuminuria in diabetic patients with early-stage diabetic nephropathy.

Abstract

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.

• Authors: Takeshi Takahashi, Miyuki Yano, Junko Minami, Tomoko Haraguchi, Naoko Koga, Kiichiro Higashi, Shozo Kobori
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 58 Issue 2 Pg. 123-9 (Nov 2002) ISSN: 0168-8227 [Print] Ireland
• PMID: 12213354 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)

Chemical References

• Glycated Hemoglobin A
• Receptor, Serotonin, 5-HT2A
• Receptors, Serotonin
• Serotonin Antagonists
• Succinates
• sarpogrelate
• Serotonin

Topics

• Albuminuria (prevention & control)
• Diabetes Mellitus, Type 2 (urine)
• Diabetic Nephropathies (prevention & control, urine)
• Female
• Follow-Up Studies
• Glycated Hemoglobin (analysis)
• Humans
• Male
• Middle Aged
• Receptor, Serotonin, 5-HT2A
• Receptors, Serotonin (drug effects, physiology)
• Reference Values
• Regression Analysis
• Serotonin (urine)
• Serotonin Antagonists (therapeutic use)
• Succinates (therapeutic use)
• Time Factors