Persistent Insulin-Sensitizing Effects of Sarpogrelate Hydrochloride, a Serotonin 2A Receptor Antagonist, in Patients With Peripheral Arterial Disease

• Published in: Circulation Journal 2006, Vol.70(11), pp.1451-1456
• Main Authors: Kokubu, Nobuaki, Tsuchihashi, Kazufumi, Yuda, Satoshi, Hase, Mamoru, Eguchi, Mariko, Wakabayashi, Takeru, Hashimoto, Akiyoshi, Nakata, Tomoaki, Miura, Tetsuji, Ura, Nobuyuki, Nagao, Kazuhiko, Tsuzuki, Masahiro, Wakabayashi, Chikashi, Shimamoto, Kazuaki
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - blood; Aged; Aged, 80 and over; Arteriosclerosis obliterans; Atherosclerosis - drug therapy; Atherosclerosis - physiopathology; Blood Pressure - drug effects; Blood Pressure - physiology; Diabetes mellitus; Female; Homeostasis - physiology; Humans; Insulin resistance; Insulin Resistance - physiology; Male; Middle Aged; Peripheral Vascular Diseases - blood; Peripheral Vascular Diseases - drug therapy; Peripheral Vascular Diseases - physiopathology; Serotonin 5-HT2 Receptor Antagonists; Serotonin antagonist; Serotonin Antagonists - pharmacology; Serotonin Antagonists - therapeutic use; Succinates - pharmacology; Succinates - therapeutic use
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.70.1451

Background There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). Methods and Results Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76±9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0±10.3 vs 9.2±2.0 μU/ml, p=0.03) and HOMA-R (4.30±2.83 vs 2.40±0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11±4.13 vs 9.64±4.37 μg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p