Pirmenol
(Synonyms: Cl-845 free base; (±)-Pirmenol) 目录号 : GC47960
A class I antiarrhythmic agent
Cas No.:68252-19-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pirmenol is a class I antiarrhythmic agent.1,2,3 It lengthens the final repolarization of action potentials in isolated rabbit ventricular myocytes and inhibits tachyarrhythmias induced by prolonged afterdepolarizations in isolated guinea pig papillary muscles when used at a concentration of 5 µM.1 Pirmenol (2.5 and 5 mg/kg) suppresses ouabain- or epinephrine-induced ventricular arrhythmias and aconitine-induced atrial arrhythmias in dogs.2,3
1.Sawanobori, T., Adaniya, H., Yamashita, S., et al.Electrophysiologic and antiarrhythmic actions of pirmenol on rabbit and guinea pig cardiac preparationsJ. Cardiovasc. Pharmacol.16(6)975-983(1990) 2.Kaplan, H.R., Mertz, T.E., and Steffe, T.J.Preclinical pharmacology of pirmenolAm. J. Cardiol.59(16)2H-9H(1987) 3.Steffe, T.J., Mertz, T.E., Hastings, S.G., et al.CL-845 (pirmenol hydrochloride): A new orally effective long-acting antiarrhythmic agentJ. Pharmacol. Exp. Ther.214(1)50-57(1980)
| Cas No. | 68252-19-7 | SDF | |
| 别名 | Cl-845 free base; (±)-Pirmenol | ||
| Canonical SMILES | OC(C1=NC=CC=C1)(C2=CC=CC=C2)CCCN3[C@H](C)CCC[C@@H]3C | ||
| 分子式 | C22H30N2O | 分子量 | 338.5 |
| 溶解度 | DMF: 2mg/mL,DMSO: 5mg/mL,Ethanol: 10mg/mL,Ethanol:PBS (pH 7.2) (1:5): 0.16mg/mL | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.9542 mL | 14.771 mL | 29.5421 mL |
| 5 mM | 0.5908 mL | 2.9542 mL | 5.9084 mL |
| 10 mM | 0.2954 mL | 1.4771 mL | 2.9542 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pirmenol: preclinical pharmacology
Angiology 1988 Mar;39(3 Pt 2):281-92.PMID:3281517doi
Pirmenol, a novel pyridinemethanol derivative, is active in a variety of experimental arrhythmic models of diverse etiology. Animal pharmacology studies showed that Pirmenol is highly efficacious whether the arrhythmias were atrial or ventricular in origin; chemically, mechanically, or electrically induced; or of the automaticity or reentrant types. The conscious coronary artery-ligated (Harris) dog model best allowed simulation of a variety of clinical situations in which Pirmenol could be used either alone or in combination. Pirmenol was highly effective by both the intravenous and oral routes, causing immediate suppression, prevention, or termination of cardiac arrhythmias. Preclinical studies in the dog showed an excellent correlation between the dose of Pirmenol, plasma levels, and antiarrhythmic efficacy. Administration of Pirmenol in the dog at intentionally accelerated infusion rates suggested a relatively wide margin of safety for Pirmenol compared with other class I agents. In vitro electrophysiologic studies in dog Purkinje fibers revealed possibly unique differences of Pirmenol from other antiarrhythmic agents. It depresses fast and slow response automaticity and its electrophysiologic effects were less variable than other class I drugs over a spectrum of potassium levels. To test the relevance of the in vitro electrophysiologic results, Pirmenol's antiarrhythmic efficacy was assessed in several in vivo dog models in which serum potassium was either increased or decreased. Studies comparing Pirmenol and disopyramide clearly showed a relative lack of serum potassium dependence for Pirmenol, suggesting a potential clinical advantage over disopyramide and other antiarrhythmics in variable potassium settings. The clinical relevance of these observations will have to be established in patients with variable potassium levels. Overall, Pirmenol compared favorably with other reference agents in efficacy and safety in extensive preclinical investigations.
Clinical pharmacology and pharmacokinetics of Pirmenol
Angiology 1988 Mar;39(3 Pt 2):293-8.PMID:3281518doi
Pirmenol hydrochloride is a promising antiarrhythmic agent with quinidine-like (Class Ia) properties presently undergoing evaluation. It's clinical pharmacology and pharmacokinetics are reviewed. The author outlines the effects of Pirmenol on the sinus node, atrial tissue, A-V node, and ventricular tissue and describes its antiarrhythmic efficacy in clinical studies to date, including his own study in 21 patients with a history of sustained ventricular tachycardia. The author summarizes the hemodynamic and pharmacokinetic studies of Pirmenol noting that its effects are relatively independent of potassium concentration. The drug's side effects profile is presented, and it is concluded that Pirmenol is well tolerated. Hypotension has not been a significant problem with intravenous Pirmenol. Precipitation or worsening of clinical heart failure appears to occur only rarely. The favorable pharmacokinetics of Pirmenol permit dosage at less frequent intervals than with procainamide, quinidine, disopyramide. Pirmenol has shown efficacy for ventricular arrhythmias even in some patients refractory to Class Ia agents. Antiarrhythmic effects appear to be correlated with plasma levels, and a well-defined therapeutic minimum has been determined.
Pirmenol: an antiarrhythmic drug with unique electrocardiographic features--a double-blind placebo-controlled comparison with quinidine
Clin Cardiol 1991 Jan;14(1):25-32.PMID:2019027DOI:10.1002/clc.4960140107.
Previous reports have stated that Pirmenol is a Class IA antiarrhythmic drug that prolongs the QT interval, but did not use computerized electrocardiography. We randomized 18 patients with frequent ventricular ectopic depolarizations to Pirmenol (8 patients) or quinidine (10 patients). Pirmenol was effective and tolerated for suppression of arrhythmia in all 7 patients treated (1 patient withdrew for personal reasons) but quinidine was effective and tolerated for 4 weeks in only 5 of 10 patients (p less than 0.05). Using computerized 12-lead electrocardiography, the mean change in PR interval from placebo to treatment was 5 +/- 18 ms for quinidine and 5 +/- 11 ms for Pirmenol (p = NS). The mean change in QRS interval was 5 +/- 14 ms for quinidine and 10 +/- 5 ms for Pirmenol (p = NS). The mean change in QT interval was 46 +/- 30 ms for quinidine and 8 +/- 9 ms for Pirmenol (p less than 0.01) and the mean change in JT interval was 41 +/- 36 ms for quinidine and -2 +/- 10 ms for Pirmenol (p less than 0.01). After the double-blind phase, 4 quinidine patients had computerized electrocardiographic intervals measured on Pirmenol; the above findings were confirmed. These electrocardiographic features of Pirmenol clearly distinguish it from quinidine, the prototype Class IA drug. However, Pirmenol has minimal effect on the PR and QRS intervals, and thus does not appear to be a Class IC drug either. Although its electrocardiographic features are closest to Class IB, its electrophysiology in isolated cells and its antiarrhythmic and side effect profile are atypical for a IB agent.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Pirmenol on action potentials and membrane currents in single atrial myocytes
Eur J Pharmacol 1998 Mar 5;344(2-3):287-97.PMID:9600665DOI:10.1016/s0014-2999(97)01579-3.
Electrophysiological effects of Pirmenol hydrochloride (Pirmenol) were investigated in single atrial myocytes obtained from rabbit and guinea-pig hearts by using a whole-cell clamp technique. Under current clamp conditions, Pirmenol (2-30 microM) prolonged action potential duration in a concentration-dependent manner without affecting resting membrane potential in rabbit atrial myocytes. However, in the presence of 4-aminopyridine (4 mM), Pirmenol (10 microM) failed to prolong the action potential duration further. Pirmenol also suppressed acetylcholine-induced hyperpolarization and action potential duration shortening, resulting in a significant prolongation of the action potential duration in the presence of acetylcholine. Under voltage clamp conditions, Pirmenol (1-1000 microM) inhibited transient outward current (I(to)) in a concentration-dependent manner. The concentration for half-maximal inhibition (IC50) of Pirmenol on I(to) was about 18 microM. Pirmenol did not show the use and frequency dependent inhibition of I(to). The voltage dependence of the steady-state inactivation of I(to) and the recovery from inactivation were not significantly affected by Pirmenol. Pirmenol accelerated the inactivation of I(to) and blocked I(to) as an exponential function of time, consistent with a time-dependent open channel blockade. Pirmenol (30 microM) did not affect the inwardly rectifying K+ current significantly, but it decreased the voltage-dependent L-type Ca2+ current by about 20%. In guinea-pig atrial myocytes, both acetylcholine and adenosine induced a specific K+ current activated by GTP-binding proteins. Pirmenol suppressed both the acetylcholine- and adenosine-induced K+ current effectively. The IC50 of Pirmenol for acetylcholine- and adenosine-induced current was about 1 and 8 microM, respectively. The present results suggest that Pirmenol prolongs the action potential duration by primarily inhibiting the transient outward current in atrial myocytes. In addition, since Pirmenol inhibits acetylcholine- and adenosine-induced K+ current, Pirmenol may effectively prolong the action potential duration in atrial myocytes under various physiological conditions as in the whole heart or ischemia.
Electrophysiologic evaluation of Pirmenol for sustained ventricular tachycardia secondary to coronary artery disease
Am J Cardiol 1986 Jul 1;58(1):86-9.PMID:3728337DOI:10.1016/0002-9149(86)90246-8.
The efficacy and electrophysiologic effects of Pirmenol were evaluated in 21 patients with a history of sustained ventricular tachycardia (VT) and coronary artery disease. Intravenous Pirmenol (0.7- to 1.1-mg/kg bolus, followed by a 35- to 40-micrograms/kg/min infusion) significantly prolonged the PR, QRS, QT and corrected QT intervals, HV interval and right ventricular effective refractory period, and shortened the sinus cycle length and atrioventricular nodal block cycle length. All 21 patients had inducible VT (20 sustained, 1 nonsustained) during programmed stimulation in the control state. After intravenous Pirmenol, 5 patients (24%) no longer had inducible VT. In those in whom VT was still inducible, the VT cycle length was prolonged significantly. The 5 patients who responded to intravenous Pirmenol were given oral Pirmenol (200 to 250 mg every 8 hours) for 1 to 3 days and retested with programmed stimulation. In 4 of these 5, VT could not be induced with oral Pirmenol administration; in 1 patient sustained VT was induced and Pirmenol therapy was discontinued. Oral Pirmenol suppressed recurrent VT during a follow-up of 315 +/- 133 days in 4 patients. However, Pirmenol therapy was discontinued in 2 patients because of possible deleterious effects (worsened heart failure in 1 patient and elevated liver function test results in 1). Thus, Pirmenol, a type IA antiarrhythmic drug, had an overall efficacy of approximately 19% in patients with sustained VT secondary to coronary artery disease.