Pinacidil

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Cat Number

API0231594

CAS Number

85371-64-8

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CAS Number

85371-64-8

EINECS

262-294-9

Storage

Store at room temperature

Synonyms

Pinacidil hydrate; DTXSID4045682; 7B0ZZH8P2W; NSC-759588; DTXCID2025682; Pinacidilum

Molecular Formula

C13H21N5O

Molecular Weight

263.34

Smiles

CC(C(C)(C)C)N=C(NC#N)NC1=CC=NC=C1.O

Appearance

White powder

Melting Point

164-165℃

Boiling Point

356.7℃ at 760 mmHg

General Description

Pinacidil is a cyanoguanidine derivative that functions as a potassium channel opener, primarily investigated for the treatment of hypertension. It is an oral vasodilator that was developed in the 1980s but never gained widespread approval in the United States. The drug acts on ATP-sensitive potassium channels in vascular smooth muscle.

Mechanism of Action

Pinacidil activates ATP-sensitive potassium channels (KATP) on the cell membrane of vascular smooth muscle cells, leading to potassium efflux and hyperpolarization. This hyperpolarization closes voltage-gated calcium channels, reducing calcium influx and decreasing intracellular calcium. The resultant relaxation of arteriolar smooth muscle produces systemic vasodilation and lowers peripheral vascular resistance without significantly affecting capacitance vessels.

Application

Although not FDA-approved, pinacidil has been used in other countries as an antihypertensive agent, particularly as add-on therapy when beta-blockers or diuretics are insufficient. The drug's lack of selectivity for vascular versus pancreatic KATP channels can also stimulate insulin release, causing hypoglycemia in susceptible individuals.

Using an isolated rat heart model of ischemia‑reperfusion, pinacidil postconditioning at concentrations of 10, 30, and 50 µmol/L improved cardiac function and mitochondrial ultrastructure, with the highest concentration being most effective. The protective effect was associated with early generation of reactive oxygen species (ROS) after reperfusion, which activated the Nrf2‑ARE signaling pathway and increased downstream antioxidant proteins. The ROS scavenger MPG abolished this protection and reduced Nrf2 activation. The authors conclude that pinacidil postconditioning works through ROS‑mediated Nrf2‑ARE activation, and 50 µmol/L provides optimal myocardial protection.

Fig. 1 Mechanism of different concentrations of pinacidil postconditioning in the rat cardiac Nrf2-ARE signaling pathway is associated with ROS. (Chen W, et al., 2021)

References

Chen W, et al. ROS‑associated mechanism of different concentrations of pinacidil postconditioning in the rat cardiac Nrf2‑ARE signaling pathway. Mol Med Rep. 2021;23(6):433.

In an isolated rat heart Langendorff model, 3 hours of cardiac arrest was induced with either Custodiol‑LP or del Nido‑LP (both containing lidocaine and pinacidil). After 90 minutes of reperfusion, both solutions produced superior left ventricular contractile recovery compared to control, but del Nido‑LP yielded significantly higher maximum and minimum dP/dt, lower coronary resistance, and reduced alpha‑fodrin degradation (a marker of myocardial injury) than Custodiol‑LP. Del Nido‑LP provides greater protection against ischemia‑reperfusion injury in this experimental setting.

Fig. 2 Left ventricular function data expressed as percentage of recovery after 3 hours. (Carmo HPD, et al., 2018)

References

Carmo HPD, et al. Lidocaine and Pinacidil Added to Blood versus Crystalloid Cardioplegic Solutions: Study in Isolated Hearts. Braz J Cardiovasc Surg. 2018;33(3):211-216.

Does Pinacidil require protection from light during storage?

Yes, it is photosensitive. Light exposure can cause photodegradation and formation of the pyridine N-oxide derivative. Store in light-resistant containers.

What is the recommended storage temperature for Pinacidil?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which can accelerate oxidative degradation of the cyanoguanidine group.

Is Pinacidil stable under high-humidity conditions?

It is slightly hygroscopic. In environments above 70% RH, it may absorb moisture and clump, but significant hydrolysis is minimal. Store with desiccant if needed.

How is the impurity pinacidil N-oxide monitored during stability?

This oxidative degradation product is quantified using a validated HPLC method, ensuring it remains below ICH qualification thresholds throughout shelf life.