Pirmenol
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MedKoo CAT#: 329526

CAS#: 68252-19-7 (free base)

Description: Pirmenol is an antiarrhythmic agent. Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart. Pirmenol is active in a variety of experimental arrhythmic models of diverse etiology and has a favorable therapeutic index compared with other class I agents. 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.

Chemical Structure

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Pirmenol
CAS# 68252-19-7 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 329526
Name: Pirmenol
CAS#: 68252-19-7 (free base)
Chemical Formula: C22H30N2O
Exact Mass: 338.24
Molecular Weight: 338.500
Elemental Analysis: C, 78.06; H, 8.93; N, 8.28; O, 4.73

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2450 Ready to ship
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Related CAS #: 78774-24-0 (racemic)   68252-19-7 (free base)   61477-94-9 (HCl)   82734-31-4 (xHCl)    

Synonym: Pirmenol; Cl 845; Cl-845; Cl845; Pirmavar.

IUPAC/Chemical Name: 4-((2R,6S)-2,6-dimethylpiperidin-1-yl)-1-phenyl-1-(pyridin-2-yl)butan-1-ol

InChi Key: APUDBKTWDCXQJA-QIDMFYOTSA-N

InChi Code: InChI=1S/C22H30N2O/c1-18-10-8-11-19(2)24(18)17-9-15-22(25,20-12-4-3-5-13-20)21-14-6-7-16-23-21/h3-7,12-14,16,18-19,25H,8-11,15,17H2,1-2H3/t18-,19+,22?

SMILES Code: OC(C1=NC=CC=C1)(C2=CC=CC=C2)CCCN3[C@H](C)CCC[C@@H]3C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Pirmenol hydrochloride inhibits IK.ACh by blocking muscarinic receptors. The IC50 of Pirmenol for inhibition of Carbachol-induced IK.ACh is 0.1 μM.
In vitro activity: Pirmenol inhibits the carbachol-induced IK.ACh in a concentration-dependent manner. Pirmenol also inhibits the GTPγS-induced current although the concentrations of Pirmenol needed to inhibit the GTPγS-induced current are much higher than those to inhibit the carbachol-induced IK.ACh. The IC50 of Pirmenol for inhibition of the GTPγS-induced currents is 30 μM. The inhibitory effect of Pirmenol on these IK.ACh is almost completely reversible and the outward current reappeared upon washout of Pirmenol. Pirmenol on the muscarinic acetylcholine receptor-operated K+ current (IK.ACh) in atrial cells and on experimental atrial fibrillation in isolated guinea-pig hearts. In isolated atrial myocytes, Pirmenol concentration dependently inhibits the IK.ACh induced by carbachol or intracellular loading of GTPγS. In Langendorff-perfused hearts Pirmenol reverses the carbachol-induced decreases in effective refractory periods and atrial fibrillation threshold. Reference: Eur J Pharmacol. 1997 Oct 29;338(1):71-4. https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)01300-9
In vivo activity: The pyridine-methanol derivative Pirmenol hydrochloride is a new antiarrhythmic agent. Single-dose studies in rodents demonstrate a 10- to 15-fold difference between the po and iv LD50 values. In rats, the po LD50 is 359.9 mg/kg and the iv LD50 is 23.6 mg/kg. Mice LD50 values are 215.5 and 20.8 mg/kg for po and iv routes, respectively. Short-term subacute iv toxicity studies in rats (2.5, 5.0, and 7.5 mg/kg) and dogs (2.5, 5, and 10 mg/kg) for 4 weeks elicite minimal reactions. Cardiac effects in dogs include drug related increases in heart rate, increases QRS duration, shortening of ST interval without evidence of cardiac tissue damage and mild local reaction at the injection site. Orally, Pirmenol is well tolerated for 13 weeks in rats receiving 25, 50, and 100 mg/kg/day while dogs given 5, 10, and 15 mg/kg/day shows anticholinergic effects at high levels (dryness of mucosae, body tremors). Heart rates are significantly accelerated only at the beginning of the study and QRS changes are seen with wide individual variations. No drug-related tissue changes are elicited in these species. Teratology studies in rats (50, 100, and 150 mg/kg) and in rabbits (10, 25, and 50 mg/kg) show no overt effect on organogenesis but embryotoxicity is seen at 150 mg/kg in rats. Reference: Toxicol Appl Pharmacol. 1980 Nov;56(2):294-301. https://www.sciencedirect.com/science/article/pii/0041008X80903014?via%3Dihub

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 5.0 14.80
Ethanol 10.0 29.50

Preparing Stock Solutions

The following data is based on the product molecular weight 338.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Watanabe Y, Hara Y, Tamagawa M, Nakaya H. Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart. Eur J Pharmacol. 1997 Oct 29;338(1):71-4. doi: 10.1016/s0014-2999(97)01300-9. PMID: 9408005.
In vivo protocol: 1. Schardein JL, Fitzgerald JE, Sanyer JL, McGuire EJ, de la Iglesia FA. Preclinical toxicology studies with a new antiarrhythmic agent: pirmenol hydrochloride (CI-845). Toxicol Appl Pharmacol. 1980 Nov;56(2):294-301. doi: 10.1016/0041-008x(80)90301-4. PMID: 7466828.

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1: Asano J, Kojima M, Sekizawa Y, Ooe T, Miyamoto N, Suzuki Y, Kohya T, Kobayashi M, Saitoh H. [An approach to complete the manual for determination of serum pirmenol levels]. Yakugaku Zasshi. 2003 Nov;123(11):981-6. Japanese. PubMed PMID: 14631760.

2: Mizuguchi Y, Ishimoto T, Kageyama N, Oishi Y, Emi S, Nagase N, Oki T. A patient responding to combined therapy with pirmenol and midodrine for refractory neurally mediated syncope complicated by prostatic hypertrophy. Cardiovasc Drugs Ther. 2004 Sep;18(5):405-8. PubMed PMID: 15717144.

3: Nakajima T, Iwasawa K, Hazama H, Omata M. Effects of pirmenol on action potentials and membrane currents in single atrial myocytes. Eur J Pharmacol. 1998 Mar 5;344(2-3):287-97. PubMed PMID: 9600665.

4: Janiczek N, Smith DE, Chang T, Sedman AJ, Stringer KA. Pharmacokinetics of pirmenol enantiomers and pharmacodynamics of pirmenol racemate in patients with premature ventricular contractions. J Clin Pharmacol. 1997 Jun;37(6):502-13. PubMed PMID: 9208357.

5: Abe H, Numata T, Hanada H, Kohshi K, Nakashima Y. Pirmenol hydrochloride-induced QT prolongation and T wave inversion on electrocardiogram during treatment for symptomatic atrial fibrillation. J UOEH. 1998 Dec 1;20(4):339-43. PubMed PMID: 9883483.

6: Janiczek N, Smith DE, Chang T, Ventura A, Mertz TE. Pharmacokinetics and pharmacodynamics of pirmenol enantiomers in coronary artery ligated dogs. J Pharm Sci. 1997 Apr;86(4):443-9. PubMed PMID: 9109046.

7: Nakagomi M, Suzuki E, Kitashima M, Iida S, Abe M, Matsuki Y, Kaneko K. Sex difference in the metabolism of pirmenol in rats. Biol Pharm Bull. 1997 Dec;20(12):1279-84. PubMed PMID: 9448104.

8: Atarashi H, Kuruma A, Ino T, Hirayama Y, Saitoh H, Hayakawa H. Clinical effects and pharmacokinetics of a single oral dose of pirmenol hydrochloride. J Cardiovasc Pharmacol. 1996 Apr;27(4):556-62. PubMed PMID: 8847873.

9: Kodama I, Ogawa S, Inoue H, Kasanuki H, Kato T, Mitamura H, Hiraoka M, Sugimoto T. Profiles of aprindine, cibenzoline, pilsicainide and pirmenol in the framework of the Sicilian Gambit. The Guideline Committee for Clinical Use of Antiarrhythmic Drugs in Japan (Working Group of Arrhythmias of the Japanese Society of Electrocardiology). Jpn Circ J. 1999 Jan;63(1):1-12. Review. PubMed PMID: 10084381.

10: Watanabe Y, Hara Y, Tamagawa M, Nakaya H. Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart. Eur J Pharmacol. 1997 Oct 29;338(1):71-4. PubMed PMID: 9408005.

11: Kasai H, Ueno K, Kusumoto M, Shibakawa M. Population pharmacokinetic analysis of pirmenol in healthy volunteers and patients with arrhythmia. Eur J Clin Pharmacol. 1999 Mar;55(1):77-8. PubMed PMID: 10206089.

12: Lee JH, Rosen MR. Electrophysiologic effects of pirmenol, its metabolite 2, and enantiomers, on cardiac Purkinje fibers. J Cardiovasc Pharmacol. 1993 Sep;22(3):416-22. PubMed PMID: 7504132.

13: Nakaya H, Hattori Y, Endou M, Gandou S, Kanno M. Electrophysiologic and anticholinergic effects of pirmenol enantiomers in guinea-pig myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1992 Nov;346(5):555-62. PubMed PMID: 1470227.

14: Salerno DM, Fifield J, Farmer C, Hodges M. Pirmenol: an antiarrhythmic drug with unique electrocardiographic features--a double-blind placebo-controlled comparison with quinidine. Clin Cardiol. 1991 Jan;14(1):25-32. PubMed PMID: 2019027.

15: Nitta J, Nogami A, Aonuma K, Akimoto H, Chung YH, Takahashi A, Iesaka Y, Marumo F, Hiraoka M. Effects of pirmenol on electrical induction of sustained ventricular tachycardia in a seven-day-old canine myocardial infarction. J Cardiovasc Pharmacol. 1991 Jan;17(1):54-60. PubMed PMID: 1708056.

16: Reichardt B, Konzen G, Hauswirth O. Pirmenol, a new antiarrhythmic drug with potassium- and sodium-channel blocking activity; a voltage-clamp study in rabbit Purkinje fibres. Naunyn Schmiedebergs Arch Pharmacol. 1990 May;341(5):462-71. PubMed PMID: 2164163.

17: Hasegawa J, Hirai S, Noguchi N, Hisatome I, Kotake H, Mashiba H. Use-dependent effects of pirmenol on Vmax and conduction in guinea-pig ventricular myocardium. Br J Pharmacol. 1990 Apr;99(4):815-9. PubMed PMID: 2361175; PubMed Central PMCID: PMC1917544.

18: Nakaya H, Tohse N, Kanno M. Frequency- and voltage-dependent depression of maximum upstroke velocity of action potentials by pirmenol in guinea pig ventricular muscles. Jpn J Pharmacol. 1988 Dec;48(4):423-34. PubMed PMID: 3244198.

19: Garg DC, Jallad NS, Singh S, Ng KF, Weidler DJ. Efficacy and pharmacokinetics of oral pirmenol, a new antiarrhythmic drug. J Clin Pharmacol. 1988 Sep;28(9):812-7. PubMed PMID: 2466056.

20: Reiter MJ. Clinical pharmacology and pharmacokinetics of pirmenol. Angiology. 1988 Mar;39(3 Pt 2):293-8. Review. PubMed PMID: 3281518.