PMID:
Br J Pharmacol. 2020 Jan 24. Epub 2020 Jan 24. PMID: 31976548
Abstract Title:
Tetramethylpyrazine, a Promising Drug for Treatment of Pulmonary Hypertension.
Abstract:
RATIONALE: Tetramethylpyrazine (TMP) is a compound isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto. TMP can also be chemosynthesized in pharmacy and has long history of proven effects in the treatment of many cardiovascular diseases.OBJECTIVES: To evaluate the potential therapeutic role of TMP on pulmonary hypertension (PH) both in experimental animal models and in clinical patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).RESULTS: TMP (100 mg•kg•d) not only prevented rats from developing experimental PH, but also ameliorated PH in three models of established PH: chronic hypoxia- (chronic-HPH), sugen/hypoxia- (SuHx-PH) or monocrotaline-(MCT-PH) induced PH. The therapeutic effect of TMP was likely due to its inhibition of intracellular calcium homeostasis in pulmonary arterial smooth muscle cells. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) significantly increased the 6-minute walk distance (6MWD, from 385±83 to 446±80 meters; p=0.04 vs baseline, p=0.001 vs control). The 1-minute heart rate recovery (HRR1) was also improved from 13±6 to 19±8 bpm (p=0.03 vs baseline, p=0.001 vs control).CONCLUSION: Our results suggest that TMP is potentially a novel, potential and inexpensive medication for treatment of PH. Clinical trial is registered with http://www.chictr.org.cn (ChiCTR-IPR-14005379).
Health Time 