Pinacidil

Pinacidil (P-1134) is a potent activator of ATP-sensitive potassium channel. Pinacidil is an antihypertensive agent hyperpolarizes vascular smooth muscle by opening K⁺ channels. Pinacidil enhances K⁺-efflux in smooth muscle. Pinacidil has vasorelaxant properties. Pinacidil is able to inhibit spontaneous tone and of reducing agonist induced contractions. Pinacidil can be studied in research area such as cardiovascular diseases^[1][2]. IC50 & Target:potassium channel^[1] In Vitro:Pinacidil (0-2 mM, 48 h) induces DNA fragmentation in a dose-dependent manner and is prominent at 1 mM in HepG2 cells^[2].
Pinacidil (1-2 mM, 36 h) induces loss of phospholipid asymmetry, resulting in appearance of phosphatidylserine on the outer layer of the plasma membrane detected by annexin-V binding in HepG2 cells^[2].
Pinacidil (1 mM, 0-48 h) induces apoptosis in a time-related manner without involvement of K_ATP channels in HepG2 cells^[2].
Pinacidil (1 mM) induces a rapid and sustained increase in [K⁺] and [Ca²⁺] in HepG2 cells^[2].
Pinacidil (1 mM, 0-60 min) induces Ca²⁺ influx through activation of the reverse mode of Na⁺/Ca²⁺ exchanger which is achieved by increased [Na⁺]_i attributed to activation of NKCC^[2].
Pinacidil (1-100 μM and 0.3-30 μM, 30 min) produces a concentration-dependent inhibition of responses to noradrenaline in rat aorta and portal vein^[3].
Pinacidil (1-100 μM) produces a concentration-dependent inhibition of responses to KCl (10-80 mmol/L) in rat aorta^[3].
Pinacidil (0.3-30 μM) produces an inhibition of responses to KCl (5-80 mmol/L) and the –log IC₅₀ against KCl (20 mmol/L) contraction was 6.2^[3].
Pinacidil (0.1-100 μM) is capable of producing almost total relaxation of tissue, and remains unaffected in the presence of Apamin (HY-P0256) (0.1 μM) in guinea-pig trachea^[3].
Pinacidil (0.3-10 μM, 4.5-7 min) abolishes spontaneous multispike complexes and mechanical activity, and results in a concentration-dependent hyperpolarization in rat portal vein^[3].
Pinacidil (0.3-30 μM, 10-35 min) produces a greater and longer lasting increase in ⁸⁶Rb exchange in the aorta than in the portal vein^[3]. In Vivo:Pinacidil (3-30 μg, i.c.v., one single dose) increases tail-flick latency dose-dependently in non- diabetic (ED₅₀ = 16.1) and diabetic mice (ED₅₀ = 22.3)^[4].
Pinacidil (10-100 μg, i.t., one single dose) produces dose-dependent and significant antinociception in diabetic mice and a dose of 100 μg results no significant antinociception in non-diabetic mice (ED₅₀ = 18.5), whereas ED₅₀ for diabetic mice is 95.6^[4].
Pinacidil (30 μg, i.c.v., one single dose) is not affected by the pretreatment of β-Funaltrexamine (HY-101318) (20 and 40 mg/kg, s.c.) on the antinociception in diabetic mice^[4].
Pinacidil (30 μg, i.t., one single dose) has a dose-dependently reduction of antinociceptive effect with β-Funaltrexamine (20 and 40 mg/kg, s.c.), and is antagonized by the pretreatment with 7-Benzylidenenaltrexon (HY-169867) (0.3 mg/kg), Naltriben (0.3 mg/kg) (HY-133717), or nor-Binaltorphimine (20 mg/kg, s.c.) (HY-117040) in diabetic mice^[4].