Pinacidil
(Synonyms: 吡那地尔,P-1134) 目录号 : GC63830
A potassium channel opener
Cas No.:60560-33-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pinacidil is a cyanoguanidine compound that acts as a potassium channel opener, activating the ATP-
1.Hermsmeyer, R.K.Pinacidil actions on ion channels in vascular muscleJ. Biomed. Sci.12(Suppl 2)S17-S22(1988) 2.Davis-Taber, R., Molinari, E.J., Altenbach, R.J., et al.[125I]A-312110, a novel high-affinity 1,4-dihydropyridine ATP-sensitive K+ channel opener: Characterization and pharmacology of bindingMol. Pharmacol.64(1)143-153(2003) 3.Coghlan, M.J., Carroll, W.A., and Gopalakrishnan, M.Recent developments in the biology and medicinal chemistry of potassium channel modulators: Update from a decade of progressJ. Med. Chem.44(11)1627-1653(2001) 4.Gollasch, M., Bychkov, R., Ried, C., et al.Pinacidil relaxes porcine and human coronary arteries by activating ATP-dependent potassium channels in smooth muscle cellsJ. Pharmacol. Exp. Ther.275(2)681-692(1995) 5.Cohen, M.L., and Kurz, K.D.Pinacidil-induced vascular relaxation: Comparison to other vasodilators and to classical mechanisms of vasodilationJ. Biomed. Sci.12(Suppl 2)S5-S9(1988) 6.Goldberg, M.R.Clinical pharmacology of pinacidil, a prototype for drugs that affect potassium channelsJ. Biomed. Sci.12(Suppl 2)S41-S47(1988)
| Cas No. | 60560-33-0 | SDF | Download SDF |
| 别名 | 吡那地尔,P-1134 | ||
| 分子式 | C13H19N5 | 分子量 | 245.32 |
| 溶解度 | DMSO : 100 mg/mL (407.63 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0763 mL | 20.3815 mL | 40.7631 mL |
| 5 mM | 0.8153 mL | 4.0763 mL | 8.1526 mL |
| 10 mM | 0.4076 mL | 2.0382 mL | 4.0763 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Pinacidil. Preclinical investigations
Drugs 1988;36 Suppl 7:4-9.PMID:3076134DOI:10.2165/00003495-198800367-00003.
Routine pharmacological screening of thiourea compounds led to the selection of pyridyl cyanoguanidines for their antihypertensive effects. From this cyanoguanidine class of compounds, P 1134 (Pinacidil) was synthesised. Pinacidil has an asymmetrical carbon atom in the pinacolyl radical and the (-) enantiomer is more active than the (+) enantiomer both in vitro and in vivo. Pinacidil is rapidly absorbed following oral administration with the time to peak plasma concentration being 0.5 to 1 hour and, for the extended release formulation, 1 to 3 and 5 to 7 hours. The antihypertensive effect of Pinacidil is proportional to the dose administered. Pyridine-N-oxide is the principal metabolite and accounts for approximately half of the dose excreted in the urine within 24 hours. In hypertensive rats and dogs, the blood pressure-lowering effect of Pinacidil is dose-dependent and linearly related to the baseline blood pressure. The haemodynamic profile is characterised by an increased cardiac output as a consequence of increased stroke volume. An increase in heart rate follows the depressor response. The fall in blood pressure is preceded and superseded by a fall in the total peripheral resistance. Preclinical haemodynamic studies suggest that Pinacidil is a directly acting precapillary vasodilator. The resting membrane potential of smooth muscle cells is approximately -60mV whereas the equilibrium potential for potassium is more negative, between -80 and -90mV. Pinacidil opens K+ channels and allows potassium to attain its equilibrium potential, resulting in hyperpolarisation of the cell at rest. A hyperpolarised cell is less prone to depolarisation, and without depolarisation there is no activation of the voltage-operated Ca2+ channels and, hence, no muscle contraction.
Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension
Drugs 1990 Jun;39(6):929-67.PMID:2196168DOI:10.2165/00003495-199039060-00008.
Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, Pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies Pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of Pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of Pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, Pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action Pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of Pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs.
Clinical pharmacology of Pinacidil, a prototype for drugs that affect potassium channels
J Cardiovasc Pharmacol 1988;12 Suppl 2:S41-7.PMID:2466178DOI:10.1097/00005344-198812002-00008.
The clinical pharmacology of potassium channel openers has been reviewed using Pinacidil as a prototype drug. When administered acutely or chronically, the hemodynamic and neuroendocrine profile is that of a peripheral arterial vasodilator. The drug produces decreases in peripheral vascular resistance, and subsequent blood pressure decreases are associated with reflex increments in heart rate. When studied, plasma catecholamines increased about twofold during chronic therapy. Plasma renin activity, however, was not increased during chronic therapy with Pinacidil monotherapy. When patients were treated with Pinacidil doses ranging from 12.5 to 75 mg b.i.d., 66.9% of patients had a decrease in supine diastolic blood pressure to below 91 mm Hg and 10 mm Hg less than baseline, whereas only 23.9% of patients had similar falls during placebo treatment. During maintenance therapy with Pinacidil, the average blood pressure during the daytime dosing interval was 137.8 +/- 1.2/83.4 +/- 0.7 mm Hg (mean +/- SEM). Titration of Pinacidil as monotherapy resulted in a characteristic adverse event profile dominated by the presence of dose-related edema. Other characteristic events included tachycardia, palpitations and headache. When Pinacidil was given to patients unresponsive to hydrochlorothiazide (25 mg b.i.d.), similar efficacy relative to placebo was noted with a change of post-dose supine diastolic blood pressure in the Pinacidil group of 13.5 +/- 0.8 mm Hg and 7.3 +/- 0.9 mm Hg in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Pinacidil on bladder muscle
Drugs 1988;36 Suppl 7:41-9.PMID:3076135DOI:10.2165/00003495-198800367-00007.
Infravesical outflow obstruction and bladder hypertrophy are often associated with bladder hyperactivity causing frequency, urge and urinary incontinence. This hyperactivity may be due to a supersensitivity to depolarising stimuli. Drugs that inhibit smooth muscle activity by opening K+ channels, resulting in hyperpolarisation, would therefore seem to be an attractive therapeutic principle. Pinacidil is an effective vasodilator classified as a K+ channel opener. The drug has been shown to effectively depress spontaneous contractile activity, the contractions induced by low (less than 40 mmol/L) concentrations of K+, carbachol and by electrical stimulation of nerves in isolated normal human bladder tissue and also in normal and hypertrophied rat bladder. The effect was more pronounced in hypertrophied detrusor. Pinacidil in concentrations inhibiting muscle activity also increased the efflux of 86Rb in bladder tissue. In vivo Pinacidil suppressed spontaneous contractile activity in rats with infravesical bladder obstruction and detrusor hypertrophy. The findings make K+ channel openers an interesting, potentially useful therapeutic principle in hyperactivity associated with bladder hypertrophy.
Mechanism of the vasodilator action of Pinacidil
Blood Vessels 1990;27(2-5):314-8.PMID:2242449DOI:10.1159/000158824.
The mechanism of the vasodilator action of Pinacidil has been studied in rat mesenteric small arteries. The results show, first, that the use of flux studies to make measurements of ion permeability requires knowledge of the membrane potential, especially as regards K+ permeability. Second, the results confirm that the vasodilator effect of Pinacidil is due to an increase in K+ permeability. Lastly, the results suggest that the K+ channels involved are sensitive to glibenclamide.