Sarpogrelate Hydrochloride

Diabetes mellitus affects the functions of large and small vessels, leading to complications broadly classified as macro-vascular complications, including peripheral arterial disease, heart disease, and stroke, and microvascular complications, including neuropathy, retinopathy, and nephropathy. Moreover, vascular dysfunction, including abnormal reactivity to endogenous substances, is often observed in patients with diabetes mellitus. Among various vasoactive substances, serotonin (5-hydroxytryptamine; 5-HT), which was first isolated from peripheral blood >70 years ago, plays a pivotal role in the vascular system. However, the role of 5-HT-mediated vascular function, including vasoconstriction, in diabetes mellitus-associated vascular complications remains unclear. In addition to the abnormal 5-HT responsiveness observed in patients with diabetes mellitus, 5-HT also contributes to diabetes-associated vasculopathy through its role in vascular wall remodeling. In this review, we first summarize the altered responses and downstream signaling pathways induced by 5-HT in large and small vessels in animal models of diabetes mellitus and in patients based on evidence from the past 30 years. We also discuss the effects of sarpogrelate, a 5-HT_2A receptor antagonist, on vascular function in diabetes mellitus and highlight the importance of blocking vascular 5-HT_2A receptors as an approach to mitigate diabetes-associated vascular dysfunction. Our overarching aim is to emphasize the importance of controlling 5-HT-mediated signaling in the vasculature to prevent and treat diabetes-associated vascular complications.

Objectives. This study evaluated the effects of sarpogrelate, a selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist, on the preservation of residual hearing and modulation of inflammatory responses following cochlear implantation (CI) in an animal model.Methods. The damaging effects of CI were simulated in male albino guinea pigs using a dummy electrode. Animals were allocated to three groups: control (n=12, dummy electrode insertion only), SPG-1004 (n=7, low-capacity pump delivering sarpogrelate), and SPG-2004 (n=6, high-capacity pump delivering sarpogrelate). Sarpogrelate was administered via osmotic pumps at two different volumes, and its effects on hearing thresholds, histological outcomes, and expression of inflammation-related genes were assessed. Hearing was evaluated using auditory brainstem response (ABR) thresholds measured at baseline (preoperatively) and at 1, 7, and 30 days postoperatively.Results. Administration of sarpogrelate via an osmotic pump resulted in significant hearing preservation across all tested frequencies at 1 month post-surgery (P<0.05) compared with the control group, which underwent dummy electrode insertion only. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were markedly reduced in the sarpogrelate-treated groups, especially in the group receiving the higher pump volume. Gene expression analysis supported these findings by showing a significant reduction in inflammation-related markers in the sarpogrelate-treated groups.Conclusion. Sarpogrelate exhibited a protective effect against the loss of residual hearing after CI, likely due to its anti-inflammatory and antifibrotic properties. In addition, the osmotic pump enabled controlled, sustained delivery of the drug over time. These findings indicate that administering sarpogrelate via an osmotic pump represents a promising pharmacological strategy for improving postoperative outcomes in CI patients by preserving residual hearing.