Disease relevance of Sarpogrelate

• CONCLUSIONS: Sarpogrelate reduces the myocardial infarct size by inhibiting the serotonin release followed by enhancement of PKC-epsilon translocation and opening of the mitochondrial KATP channel in ischemic myocytes [1].
• Sarpogrelate, a selective 5-HT(2A) antagonist, has been introduced clinically as a therapeutic agent for the treatment of ischemic diseases associated with thrombosis [2].
• The present study examined the effect of a selective 5-HT(2A) receptor antagonist, sarpogrelate, on hyperalgesia and allodynia induced by thermal injury in rats [3].
• CONCLUSIONS: These data suggest that sarpogrelate could be used as a therapeutic agent to inhibit serotonin-induced neointimal hyperplasia and improve patency of coronary artery bypass grafts [4].
• Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese A(y) mice, whereas it did not increase plasma adiponectin levels [5].

Psychiatry related information on Sarpogrelate

• However, sarpogrelate and ketanserin, 5-HT 2A receptor antagonists, significantly elevated the pain threshold in the hyperalgesic hind limb, but not in the normal hind limb [6].

High impact information on Sarpogrelate

• OBJECTIVES: The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina [7].
• Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina [7].
• We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate [7].
• Induction of indefinite survival of fully mismatched cardiac allografts and generation of regulatory cells by sarpogrelate hydrochloride [8].
• Intense expression of P-selectin was found on the endothelium of the pulmonary arteries in the placebo group, and it was markedly attenuated in the sarpogrelate-treated group [9].

Chemical compound and disease context of Sarpogrelate

• Effects of sarpogrelate hydrochloride in a patient with chronic graft-versus-host disease: a case report [10].
• The effect of a 5HT2 receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function in Buerger's disease [11].
• The effect of the serotonin (5HT(2)) receptor antagonist, sarpogrelate, was compared with that of the selective thrombin inhibitor, argatroban, in modified tissue plasminogen activator (mt-PA)-induced thrombolysis using two laser-induced thrombosis models reflecting different levels of vascular endothelial cell damage [12].
• The 5-HT2 receptor antagonist sarpogrelate reduces urinary and plasma levels of thromboxane A2 and urinary albumin excretion in non-insulin-dependent diabetes mellitus patients [13].

Biological context of Sarpogrelate

• Inhibition of serotonin-induced vascular smooth muscle cell proliferation by sarpogrelate [14].
• In SHR rats bilateral injection of sarpogrelate produced an increase in blood pressure, although it did not alter baroreceptor-evoked changes in heart rate [15].
• Sarpogrelate acted at the G1 phase of the cell cycle [4].
• 5-HT produced a dose-dependent increase in platelet aggregation in non-diabetic and sarpogrelate treated diabetic rats [16].
• These results indicate that sarpogrelate improves insulin resistance in type 2 diabetic rats [17].

Anatomical context of Sarpogrelate

• Furthermore, the blood flow in the ischemic hindlimbs was increased by the administration of sarpogrelate, a selective 5-HT(2A)-receptor antagonist [18].
• Although other cytokines such as platelet-derived growth factor and endothelin also induced DNA, RNA, and protein synthesis in rat aortic smooth muscle cells, cell proliferation was not influenced by sarpogrelate, even at large pharmacological concentrations (10 microM) [14].
• Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency [4].
• Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells [19].
• No data regarding the effects of sarpogrelate on neutrophil functions are available despite the possible clinical concern [20].

Associations of Sarpogrelate with other chemical compounds

• CONCLUSIONS: Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals [7].
• Bilateral injection of sarpogrelate did not alter blood pressure or reflex changes in heart rate in response to phenylephrine-induced increases in blood pressure or nitroprusside-induced decreases in blood pressure [15].
• CONCLUSIONS: These findings suggest that sarpogrelate (even at clinically relevant concentrations) is able to inhibit O2- production by neutrophils [20].
• This compound was a more potent inhibitor of ex vivo 5-HT-induced platelet aggregation than compound 3, which was previously shown to be more potent than ketanserin (1) and sarpogrelate (2a) [21].
• In addition to these effects, sarpogrelate and M-1, but not ketanserin produced an increase in the basal IP level of alpha(1d)-expressed CHO cells, although the increase was less than that of phenylephrine [22].

Gene context of Sarpogrelate

• Circulating plasma levels of PDGF and sP-selectin in 13 patients with ASO after 1 week of medication with sarpogrelate were significantly lower than those before medication [23].
• 5-HT(2) receptor blocker sarpogrelate prevents downregulation of antiapoptotic protein Bcl-2 and protects the heart against ischemia-reperfusion injury [24].
• Significant decreases in levels of PDGF, sP-selectin and TGF-beta1 released from platelets in response to 5 micromol/l ADP and 1 microg/ml collagen after taking of sarpogrelate were found [23].
• Our data suggest that by reducing circulating IL-18 levels, sarpogrelate treatment may contribute to the inhibition of arteriosclerosis obliterans progression in patients with diabetes [25].
• Both sarpogrelate and M-1 had no affinity for 5-HT3 receptor subtypes [26].

Analytical, diagnostic and therapeutic context of Sarpogrelate

• The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment [7].
• Systemic administration of 5-HT2A receptor antagonist (Sarpogrelate HCI) produced analgesic effects on thermal hyperalgesia caused by peripheral inflammation, but failed to attenuate thermal hyperalgesia in chronic constriction injury model [27].
• Treating the rats with sarpogrelate during reperfusion also showed similar results [24].
• Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d sarpogrelate treatment of 4 weeks (HTB group) and without (control group) [17].
• The patients were randomly allocated to two groups, including those receiving oral administration of 200 mg of sarpogrelate (SPG, 8 patients, age 61 +/- 6 years) and those receiving no medication (controls, 7 patients, age 57 +/- 8 years) [28].

References