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{{drugbox |
{{Drugbox
| IUPAC_name =  
| Verifiedfields = changed
| image = Prajmaline_svg.png
| verifiedrevid = 464212942
| IUPAC_name = (4α,16''R'',17''R'',21α)-4-propylajmalan-4-ium-17,21-diol
| image = Prajmaline.svg
 
<!--Clinical data-->
| tradename = 
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4  / S8 -->
| legal_UK = <!-- GSL        / P      / POM / CD -->
| legal_US = <!-- OTC                  / Rx-only  -->
| legal_status = 
| routes_of_administration = 
 
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion = 
 
<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 35080-11-6
| CAS_number = 35080-11-6
| ATC_prefix = C01
| ATC_prefix = C01
| ATC_suffix = BA08
| ATC_suffix = BA08
| PubChem = 37042
| PubChem = 37042
| DrugBank =  
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| C = 23 | H = 33 | N = 2 | O = 2 | charge = +
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 16735977
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 75934UD4GJ
 
<!--Chemical data-->
| C=23 | H=33 | N=2 | O=2 | charge = +  
| molecular_weight = 369.520 g/mol
| molecular_weight = 369.520 g/mol
| bioavailability =  
| smiles = O[C@@H]6C4[C@@H]2C[C@]65c1ccccc1N(C)[C@H]5[C@@H]3C[C@H]4[C@H](CC)[C@@H](O)[N+]23CCC
| protein_bound =  
| InChI = 1/C23H33N2O2/c1-4-10-25-17-11-14(13(5-2)22(25)27)19-18(25)12-23(21(19)26)15-8-6-7-9-16(15)24(3)20(17)23/h6-9,13-14,17-22,26-27H,4-5,10-12H2,1-3H3/q+1/t13-,14-,17-,18-,19?,20-,21+,22+,23+,25?/m0/s1
| metabolism =
| InChIKey = UAUHEPXILIZYCU-UUEXUKNBBY
| elimination_half-life =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| excretion =
| StdInChI = 1S/C23H33N2O2/c1-4-10-25-17-11-14(13(5-2)22(25)27)19-18(25)12-23(21(19)26)15-8-6-7-9-16(15)24(3)20(17)23/h6-9,13-14,17-22,26-27H,4-5,10-12H2,1-3H3/q+1/t13-,14-,17-,18-,19?,20-,21+,22+,23+,25?/m0/s1
| pregnancy_AU =  <!-- A / B1 / B2 / B3 / C / D / X -->
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_US =  <!-- A / B            / C / D / X -->
| StdInChIKey = UAUHEPXILIZYCU-UUEXUKNBSA-N
| pregnancy_category =
| legal_AU =     <!-- Unscheduled / S2 / S3 / S4  / S8 -->
| legal_UK =      <!-- GSL        / P      / POM / CD -->
| legal_US =      <!-- OTC                  / Rx-only  -->
| legal_status =  
| routes_of_administration =  
}}
}}
__NOTOC__
__NOTOC__
{{SI}}
{{CMG}}
{{CMG}}


{{Editor Join}}
==Overview==
'''Prajmaline''' (Neo-gilurythmal)<ref name="Jan">Janicki, K., J. Orski, and J. Kakol. "Antiarrhythmic Effects of Prajmaline (Neo-Gilurythmal) in Stable Angina Pectoris." Przegl Lek 52.10 (1995): 485-91. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/8834838>.</ref> is a class Ia [[antiarrhythmic agent]]<ref name="Weir">Weirich, J., and H. Antoni. "Differential Analysis of the Frequency-Dependent Effects of Class 1 Antiarrhythmic Drugs According to Periodical Ligand Binding." Journal of Cardiovascular Pharmacology 15.6 (1990): 998-1009. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1694924>.</ref> which has been available since the 1970s.<ref name="Kopp">Koppel, Claus, Ursula Oberdisse, and Gerhard Heinemeyer. "Clinical Course and Outcome in Class IC Antiarrhythmic Overdose." Clinical Toxicology 28.4 (1990): 433-44. Web. 6 Feb. 2011. <http://informahealthcare.com/doi/pdf/10.3109/15563659009038586>.</ref> Class Ia drugs increase the time one action potential lasts in the heart.<ref>Milne, J. R., K. J. Hellestrand, R. S. Bexton, P. J. Burnett, N. Debbas, and A. Camm. "Class 1 Antiarrhythmic Drugs — Characteristic Electrocardiographic Differences When Assessed by Atrial and Ventricular Pacing." European Heart Journal 5 (1984): 99-107. Web. 6 Feb. 2011. <http://eurheartj.oxfordjournals.org/content/5/2/99.full.pdf>.</ref> Prajmaline is a semi-synthetic propyl derivative of [[ajmaline]], with a higher bioavailability than its predecessor.<ref>Hinse, C., and J. Stöckigt. "The Structure of the Ring-opened N Beta-propyl-ajmaline (Neo-Gilurytmal) at Physiological PH Is Obviously Responsible for Its Better Absorption and Bioavailability When Compared with Ajmaline (Gilurytmal)." Pharmazie 55.7 (2000): 531-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/10944783>.</ref> It acts to stop [[arrhythmias]] of the heart through a frequency-dependent block of cardiac sodium channels.<ref name="Weir"/>
 
==Mechanism==
Prajmaline causes a resting block in the heart.<ref name="Lang">Langenfeld, H., J. Weirich, C. Köhler, and K. Kochsiek. "Comparative Analysis of the Action of Class I Antiarrhythmic Drugs (Lidocaine, Quinidine, and Prajmaline) in Rabbit Atrial and Ventricular Myocardium." Journal of Cardiovascular Pharmacology 15.2 (1990): 338-45. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1689432>.</ref> A resting block is the depression of a person's Vmax after a resting period. This effect is seen more in the atrium than the ventricle.<ref name="Lang"/> The effects of some Class I antiarrhythmics are only seen in a patient who has a normal heart rate (~1&nbsp;Hz).<ref name="Langen">Langenfeld, H., C. Köhler, J. Weirich, M. Kirstein, and K. Kochsiek. "Reverse Use Dependence of Antiarrhythmic Class Ia, Ib, and Ic: Effects of Drugs on the Action Potential Duration?" Pacing and Clinical Electrophysiology 2nd ser. 15.11 (1992): 2097-102. Web. 6 Feb. 2011. <http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8159.1992.tb03028.x/pdf>.</ref> This is due to the effect of a phenomenon called reverse use dependence.<ref name="Langen"/> The higher the heart rate, the less effect Prajmaline will have.
 
==Uses==
The drug Prajmaline has been used to treat a number of cardiac disorders. These include: coronary artery disease,<ref name="Sow">Sowton, E., I. D. Sullivan, and J. C. P. Crick. "Acute Haemodynamic Effects of Ajmaline and Prajmaline in Patients with Coronary Heart Disease." European Journal of Clinical Pharmacology 26.2 (1984): 147-50. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/6723753>.</ref><ref name="Hand">Handler, C. E., A. Kritikos, I. D. Sullivan, A. Charalambakis, and E. Sowton. "Effects of Oral Prajmaline Bitartrate on Exercise Test Responses in Patients with Coronary Artery Disease." European Journal of Clinical Pharmacology 28.4 (1985): 371-74. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/4029242>.</ref> angina,<ref name="Sow"/><ref name="Hand"/> paroxysmal tachycardia and Wolff–Parkinson–White syndrome.<ref name="Jan"/> Prajmaline has been indicated in the treatment of certain disorders where other antiarrhythmic drugs were not effective.<ref name="Jan"/>
 
==Administration==
Prajmaline can be administered orally,<ref name="Hand"/> parenterally<ref name="Sow"/> or intravenously.<ref name="Sow"/> Three days after the last dose, a limited effect has been observed. Therefore it has been suggested that treatment of arrhythmias with Prajmaline must be continuous to see acceptable results.<ref name="Jan"/>


==Pharmacokinetics==
The main metabolites of Prajmaline are: 21-carboxyprajmaline and hydroxyprajmaline. Twenty percent of the drug is excreted in the urine unchanged.


Daily therapeutic dose is 40–80&nbsp;mg.
Distribution half-life is 10 minutes.
Plasma protein binding is 60%.
Oral bioavailability is 80%.
Elimination half-life is 6 hours.
Volume of distribution is 4-5 L/kg.
<ref name="Kopp"/>


==Side Effects==
There are no significant adverse side-effects of Prajmaline when taken alone and with a proper dosage.<ref name="Jan"/><ref name="Sow"/><ref name="Hand"/>  Patients who are taking other treatments for their symptoms (e.g. beta blockers and nifedipine) have developed minor transient conduction defects when given Prajmaline.<ref name="Sow"/>


==Overview==
==Overdose==
'''Prajmaline''' is a class 1a [[antiarrhythmic agent]].
An overdose of Prajmaline is possible. The range of symptoms seen during a Prajmaline overdose include: no symptoms, nausea/vomiting, bradycardia, tachycardia, hypotension, and death.<ref name="Kopp"/>
 
==Other Potential Uses==
Due to Prajmaline's sodium channel-blocking properties, it has been shown to protect rat white matter from anoxia (82 +/- 15%).<ref name="Stys">Stys, PK. "Protective Effects of Antiarrhythmic Agents against Anoxic Injury in CNS White Matter." Journal of Cerebral Blood Flow & Metabolism 15.3 (1995): 425-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7714000>.</ref><ref name="Malek">Malek, S., J. Adorante, and P. Stys. "Differential Effects of Na-K-ATPase Pump Inhibition, Chemical Anoxia, and Glycolytic Blockade on Membrane Potential of Rat Optic Nerve." Brain Research 1037.1-2 (2005): 171-79.</ref> The concentration used causes little suppression of the preanoxic response.<ref name="Stys"/><ref name="Malek"/>


==References==
{{Reflist}}


{{Antiarrhythmic agents}}
{{Antiarrhythmic agents}}


[[Category:Antiarrhythmic agents]]
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Revision as of 22:00, 23 July 2014

Prajmaline
File:Prajmaline.svg
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E number{{#property:P628}}
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Chemical and physical data
FormulaC23H33N2O2+
Molar mass369.520 g/mol
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Prajmaline (Neo-gilurythmal)[1] is a class Ia antiarrhythmic agent[2] which has been available since the 1970s.[3] Class Ia drugs increase the time one action potential lasts in the heart.[4] Prajmaline is a semi-synthetic propyl derivative of ajmaline, with a higher bioavailability than its predecessor.[5] It acts to stop arrhythmias of the heart through a frequency-dependent block of cardiac sodium channels.[2]

Mechanism

Prajmaline causes a resting block in the heart.[6] A resting block is the depression of a person's Vmax after a resting period. This effect is seen more in the atrium than the ventricle.[6] The effects of some Class I antiarrhythmics are only seen in a patient who has a normal heart rate (~1 Hz).[7] This is due to the effect of a phenomenon called reverse use dependence.[7] The higher the heart rate, the less effect Prajmaline will have.

Uses

The drug Prajmaline has been used to treat a number of cardiac disorders. These include: coronary artery disease,[8][9] angina,[8][9] paroxysmal tachycardia and Wolff–Parkinson–White syndrome.[1] Prajmaline has been indicated in the treatment of certain disorders where other antiarrhythmic drugs were not effective.[1]

Administration

Prajmaline can be administered orally,[9] parenterally[8] or intravenously.[8] Three days after the last dose, a limited effect has been observed. Therefore it has been suggested that treatment of arrhythmias with Prajmaline must be continuous to see acceptable results.[1]

Pharmacokinetics

The main metabolites of Prajmaline are: 21-carboxyprajmaline and hydroxyprajmaline. Twenty percent of the drug is excreted in the urine unchanged.

Daily therapeutic dose is 40–80 mg. Distribution half-life is 10 minutes. Plasma protein binding is 60%. Oral bioavailability is 80%. Elimination half-life is 6 hours. Volume of distribution is 4-5 L/kg. [3]

Side Effects

There are no significant adverse side-effects of Prajmaline when taken alone and with a proper dosage.[1][8][9] Patients who are taking other treatments for their symptoms (e.g. beta blockers and nifedipine) have developed minor transient conduction defects when given Prajmaline.[8]

Overdose

An overdose of Prajmaline is possible. The range of symptoms seen during a Prajmaline overdose include: no symptoms, nausea/vomiting, bradycardia, tachycardia, hypotension, and death.[3]

Other Potential Uses

Due to Prajmaline's sodium channel-blocking properties, it has been shown to protect rat white matter from anoxia (82 +/- 15%).[10][11] The concentration used causes little suppression of the preanoxic response.[10][11]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Janicki, K., J. Orski, and J. Kakol. "Antiarrhythmic Effects of Prajmaline (Neo-Gilurythmal) in Stable Angina Pectoris." Przegl Lek 52.10 (1995): 485-91. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/8834838>.
  2. ↑ 2.0 2.1 Weirich, J., and H. Antoni. "Differential Analysis of the Frequency-Dependent Effects of Class 1 Antiarrhythmic Drugs According to Periodical Ligand Binding." Journal of Cardiovascular Pharmacology 15.6 (1990): 998-1009. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1694924>.
  3. ↑ 3.0 3.1 3.2 Koppel, Claus, Ursula Oberdisse, and Gerhard Heinemeyer. "Clinical Course and Outcome in Class IC Antiarrhythmic Overdose." Clinical Toxicology 28.4 (1990): 433-44. Web. 6 Feb. 2011. <http://informahealthcare.com/doi/pdf/10.3109/15563659009038586>.
  4. ↑ Milne, J. R., K. J. Hellestrand, R. S. Bexton, P. J. Burnett, N. Debbas, and A. Camm. "Class 1 Antiarrhythmic Drugs — Characteristic Electrocardiographic Differences When Assessed by Atrial and Ventricular Pacing." European Heart Journal 5 (1984): 99-107. Web. 6 Feb. 2011. <http://eurheartj.oxfordjournals.org/content/5/2/99.full.pdf>.
  5. ↑ Hinse, C., and J. Stöckigt. "The Structure of the Ring-opened N Beta-propyl-ajmaline (Neo-Gilurytmal) at Physiological PH Is Obviously Responsible for Its Better Absorption and Bioavailability When Compared with Ajmaline (Gilurytmal)." Pharmazie 55.7 (2000): 531-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/10944783>.
  6. ↑ 6.0 6.1 Langenfeld, H., J. Weirich, C. Köhler, and K. Kochsiek. "Comparative Analysis of the Action of Class I Antiarrhythmic Drugs (Lidocaine, Quinidine, and Prajmaline) in Rabbit Atrial and Ventricular Myocardium." Journal of Cardiovascular Pharmacology 15.2 (1990): 338-45. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/1689432>.
  7. ↑ 7.0 7.1 Langenfeld, H., C. Köhler, J. Weirich, M. Kirstein, and K. Kochsiek. "Reverse Use Dependence of Antiarrhythmic Class Ia, Ib, and Ic: Effects of Drugs on the Action Potential Duration?" Pacing and Clinical Electrophysiology 2nd ser. 15.11 (1992): 2097-102. Web. 6 Feb. 2011. <http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8159.1992.tb03028.x/pdf>.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Sowton, E., I. D. Sullivan, and J. C. P. Crick. "Acute Haemodynamic Effects of Ajmaline and Prajmaline in Patients with Coronary Heart Disease." European Journal of Clinical Pharmacology 26.2 (1984): 147-50. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/6723753>.
  9. ↑ 9.0 9.1 9.2 9.3 Handler, C. E., A. Kritikos, I. D. Sullivan, A. Charalambakis, and E. Sowton. "Effects of Oral Prajmaline Bitartrate on Exercise Test Responses in Patients with Coronary Artery Disease." European Journal of Clinical Pharmacology 28.4 (1985): 371-74. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/4029242>.
  10. ↑ 10.0 10.1 Stys, PK. "Protective Effects of Antiarrhythmic Agents against Anoxic Injury in CNS White Matter." Journal of Cerebral Blood Flow & Metabolism 15.3 (1995): 425-32. PubMed. Web. 6 Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/7714000>.
  11. ↑ 11.0 11.1 Malek, S., J. Adorante, and P. Stys. "Differential Effects of Na-K-ATPase Pump Inhibition, Chemical Anoxia, and Glycolytic Blockade on Membrane Potential of Rat Optic Nerve." Brain Research 1037.1-2 (2005): 171-79.

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