Mephentermine

Last updated

Mephentermine
Mephentermine.svg
Clinical data
Trade names Wyamine, Fentermin, Mephentine [1] [2] [3]
Other namesMephenterdrine; Mephetedrine; N-Methylphentermine; N,α,α-Trimethylphenethylamine; N,α,Dimethylampetamine; α-Methylmethamphetamine
Routes of
administration 		Intravenous, intramuscular, oral, inhalation [4] [5]
ATC code
Legal status
Legal status
Identifiers
  • N,2-dimethyl-1-phenylpropan-2-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.002.638 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H17N
Molar mass 163.264 g·mol−1
3D model (JSmol)
  • N(C(Cc1ccccc1)(C)C)C
  • InChI=1S/C11H17N/c1-11(2,12-3)9-10-7-5-4-6-8-10/h4-8,12H,9H2,1-3H3 Yes check.svgY
  • Key:RXQCGGRTAILOIN-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Mephentermine, sold under the brand name Wyamine among others, is a sympathomimetic medication which was previously used in the treatment of low blood pressure but is mostly no longer marketed. [6] [5] [4] [7] [8] It is used by injection into a vein or muscle, by inhalation, and by mouth. [4] [5]

Contents

Side effects of mephentermine include dry mouth, sedation, reflex bradycardia, arrhythmias, and hypertension. [4] Mephentermine induces the release of norepinephrine and dopamine and is described as an indirectly acting sympathomimetic and psychostimulant. [4] Its sympathomimetic effects are mediated by indirect activation of α- and β-adrenergic receptors. [5] Chemically, it is a substituted phenethylamine and amphetamine and is closely related to phentermine and methamphetamine. [4] [9] [1]

Mephentermine was first described and introduced for medical use by 1952. [10] It was discontinued in the United States between 2000 and 2004. [2] [7] The medication appears to remain available only in India. [4] [7] [8] Misuse of mephentermine for recreational and performance-enhancing purposes has been increasingly encountered in modern times, especially in India. [11] [4]

Medical uses

For maintenance of blood pressure in hypotensive states, the dose for adults is 30 to 45 mg as a single dose, repeated as necessary or followed by intravenous infusion of 0.1% mephentermine in 5% dextrose, with the rate and duration of administration depending on the patient's response.[ citation needed ]

For hypotension secondary to spinal anesthesia in obstetric patients, the dose for adults is 15 mg as a single dose, repeated if needed. The maximum dose 30 mg.[ citation needed ]

Mephentermine has also been used as a decongestant. [6] [5]

Available forms

Mephentermine is available in the form of 15 and 30 mg/mL solutions for intravenous infusion or intramuscular injection and in the form of 10 mg oral tablets. [4] It has also been available in the form of inhalers. [5]

Contraindications

Low blood pressure caused by phenothiazines, hypertension, and pheochromocytoma.[ citation needed ]

Patients receiving monoamine oxidase inhibitors.[ citation needed ]

For shock due to loss of blood or fluid, give fluid replacement therapy primarily, cardiovascular disease, hypertension, hyperthyroidism, chronic illnesses, lactation, pregnancy, skin dryness. headache.[ citation needed ]

Side effects

The most common side effects of mephentermine are drowsiness, incoherence, hallucinations, convulsions, slow heart rate (reflex bradycardia). Fear, anxiety, restlessness, tremor, insomnia, confusion, irritability, and psychosis. Nausea, vomiting, reduced appetite, urinary retention, dyspnea, weakness, and neck pain.[ citation needed ]

Potentially fatal reactions are due to atrioventricular block, central nervous system stimulation, cerebral hemorrhage, pulmonary edema, and ventricular arrhythmias.[ citation needed ]

Interactions

Mephentermine antagonizes effect of agents that lower blood pressure. Severe hypertension may occur with monoamine oxidase inhibitors and possibly tricyclic antidepressants. Additive vasoconstricting effects occur with ergot alkaloids, and oxytocin.[ citation needed ]

Potentially fatal drug interactions are the risk of abnormal heart rhythm in people undergoing anesthesia with cyclopropane and halothane.[ citation needed ]

Pharmacology

Pharmacodynamics

Mephentermine is thought to act as a releasing agent of norepinephrine and dopamine. [4] It is described as an indirectly acting sympathomimetic, cardiac stimulant, adrenergic, vasoconstrictor, antihypotensive agent, and psychostimulant. [1] [2] [8] [4] Its sympathomimetic effects are mediated by indirect activation of α- and β-adrenergic receptors. [5] [6]

Mephentermine appears to act by indirect stimulation of β-adrenergic receptors through causing the release of norepinephrine from its storage sites. It has a positive inotropic effect on the myocardium. AV conduction and refractory period of AV node is shortened with an increase in ventricular conduction velocity. It dilates arteries and arterioles in the skeletal muscle and mesenteric vascular beds, leading to an increase in venous return.[ citation needed ]

Pharmacokinetics

Its onset of action is 5 to 15 minutes with intramuscular injection and is immediate with intravenous administration.[ citation needed ] Its duration of action is 4 hours with intramuscular injection and 30 minutes with intravenous administration.[ citation needed ]

Mephentermine, along with phentermine, is known to be produced as a metabolite of the orally administered local anesthetic oxetacaine (oxethazaine). [12] [13]

Chemistry

Mephentermine, also known as N,α,α-trimethylphenethylamine or N,α-dimethylampetamine, is a phenethylamine and amphetamine derivative. [9] [1] [4] It is the N-methylated analogue of phentermine (α-methylamphetamine) and is also known as N-methylphentermine. [9] [1] In addition, mephentermine is the α-methylated analogue of methamphetamine or the α,α-dimethylated derivative of amphetamine. [9] [4]

Synthesis

Mephentermine can by synthesized beginning with a Henry reaction between benzaldehyde (1) and 2-nitropropane (2) to give 2-methyl-2-nitro-1-phenylpropan-1-ol (3). [14] The nitro group is reduced with zinc in sulfuric acid giving 2-phenyl-1,1-dimethylethanolamine (4). Imine formation by dehydration with benzaldehyde gives (5). Alkylation with iodomethane leads to (6). Halogenation with thionyl chloride gives (7). Lastly, a Rosenmund reduction completes the synthesis of mephentermine (8).

Synthesis of mephentermine Mephentermine synthesis.svg
Synthesis of mephentermine

Mephentermine can also be synthesized by condensation of phentermine with benzaldehyde to get a Schiff base which can be alkylated with methyl iodide to give mephentermine. [15]

History

Mephentermine was first described in the literature and was introduced for medical use under the brand name Wyamine by 1952. [10] It was discontinued in the United States between 2000 and 2004. [2] [7]

Society and culture

Names

Mephentermine is the generic name of the drug and its INN Tooltip International Nonproprietary Name, BAN Tooltip British Approved Name, and DCF Tooltip Dénomination Commune Française. [1] [2] [3] In the case of the sulfate salt, its USAN Tooltip United States Adopted Name is mephentermine sulfate and its BANM Tooltip British Approved Name is mephentermine sulphate. [3] [2] [7] Synonyms of mephentermine include mephetedrine and mephenterdrine. [2] [7] [9] Brand names of mephentermine include Wyamine (US Tooltip United States), Fentermin (PT Tooltip Portugal), and Mephentine (IN Tooltip India). [1] [2] [7]

Availability

Mephentermine is no longer available in the United States and remains available in few or no other countries. [7] [8] However, it appears to remain available in India. [8] [7] It has also remained available in Brazil for use in veterinary medicine. [5]

Recreational use

Misuse of mephentermine for recreational and/or performance-enhancing purposes has been reported along with addiction and dependence and serious health complications. [16] [17] [18] [19] [5] [20] [21] [22] [11] [23] [24] [25] [26] [4] It has been especially encountered in India, the only country in which mephentermine appears to remain available for medical use. [4] [7] [8]

Exercise and sports

Mephentermine has been used as a performance-enhancing drug in exercise and sports. [6] [11] [4] It is on the World Anti-Doping Agency (WADA) list of prohibited substances. [27] [26]

Research

Mephentermine was evaluated in the treatment of congestive heart failure in one small clinical study but was found to be ineffective. [28] [29]

Veterinary use

Mephentermine has been used in veterinary medicine in Brazil under the brand names Potenay and Potemax. [5]

Related Research Articles

<span class="mw-page-title-main">Pseudoephedrine</span> Pharmaceutical drug

Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of low blood pressure. At higher doses, it may produce various additional effects, including psychostimulant, appetite suppressant, and performance-enhancing effects. In relation to this, non-medical use of pseudoephedrine has been encountered. The medication is taken by mouth.

<span class="mw-page-title-main">Beta blocker</span> Medications for abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<span class="mw-page-title-main">Ephedrine</span> Medication and stimulant

Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks for people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Propranolol</span> Beta blocker drug

Propranolol is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.

<span class="mw-page-title-main">Atenolol</span> Beta blocker medication

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality in those with the condition. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">5-MeO-aMT</span> Chemical compound

5-MeO-αMT or 5-methoxy-α-methyltryptamine, α,O-Dimethylserotonin (Alpha-O) is a potent psychedelic tryptamine. It is soluble in ethanol.

<span class="mw-page-title-main">Sympathomimetic drug</span> Substance that mimics effects of catecholamines

Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among numerous others, is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, applied to the skin, or as a rectal suppository.

<span class="mw-page-title-main">Oxymetazoline</span> Topical decongestant

Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eye drops to treat eye redness due to minor irritation, and as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three days may cause congestion to recur or worsen, resulting in physical dependence.

<span class="mw-page-title-main">Synephrine</span> Chemical compound

Synephrine, or, more specifically, p-synephrine, is an alkaloid, occurring naturally in some plants and animals, and also in approved drugs products as its m-substituted analog known as neo-synephrine. p-Synephrine and m-synephrine are known for their longer acting adrenergic effects compared to epinephrine and norepinephrine. This substance is present at very low concentrations in common foodstuffs such as orange juice and other orange products, both of the "sweet" and "bitter" variety. The preparations used in traditional Chinese medicine (TCM), also known as Zhi Shi (枳实), are the immature and dried whole oranges from Citrus aurantium. Extracts of the same material or purified synephrine are also marketed in the US, sometimes in combination with caffeine, as a weight-loss-promoting dietary supplement for oral consumption. While the traditional preparations have been in use for millennia as a component of TCM-formulas, synephrine itself is not an approved over the counter drug. As a pharmaceutical, m-synephrine (phenylephrine) is still used as a sympathomimetic, mostly by injection for the treatment of emergencies such as shock, and rarely orally for the treatment of bronchial problems associated with asthma and hay-fever.

<span class="mw-page-title-main">Pemoline</span> Stimulant, used in the treatment of ADHD

Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries due to rare but serious problems with liver toxicity. The medication was taken by mouth.

<span class="mw-page-title-main">Isoprenaline</span> Medication for slow heart rate

Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic medication which is used in the treatment of acute bradycardia, heart block, and rarely for asthma, among other indications. It is used by injection into a vein, muscle, fat, or the heart, by inhalation, and in the past under the tongue or into the rectum.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Droperidol</span> Antidopaminergic drug

Droperidol is an antidopaminergic drug used as an antiemetic and as an antipsychotic. Droperidol is also often used as a rapid sedative in intensive-care treatment, and where "agitation aggression or violent behavior" are present.

<span class="mw-page-title-main">Metaraminol</span> Antihypotensive medication

Metaraminol, also known as metaradrine and sold under the brand names Aramine and Pressonex among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension, particularly as a complication of anesthesia. It is given by intramuscular or intravenous administration.

<span class="mw-page-title-main">Oxyfedrine</span> Chemical compound

Oxyfedrine, sold under the brand names Ildamen and Myofedrin among others, is a sympathomimetic agent and coronary vasodilator which is used in the treatment of coronary heart disease, angina pectoris, and acute myocardial infarction. It is taken by mouth or intravenously.

<span class="mw-page-title-main">Tiapride</span> Antipsychotic medication

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects.

<span class="mw-page-title-main">Methylephedrine</span> Chemical compound

Methylephedrine, sold under the brand name Metheph among others, is a sympathomimetic medication described as an antiasthmatic agent and used to treat coughing and nasal congestion. It is reported to be used in various over-the-counter cough and cold preparations throughout the world, including Japan.

References

  1. 1 2 3 4 5 6 7 Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 968. ISBN   978-1-4757-2085-3 . Retrieved 28 July 2024.
  2. 1 2 3 4 5 6 7 8 Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 647. ISBN   978-3-88763-075-1 . Retrieved 28 July 2024.
  3. 1 2 3 Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 175. ISBN   978-94-011-4439-1 . Retrieved 28 July 2024.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Malik YK, Bhardwaj A, Ray A, Malik B, Gupta R (2023). ""Mephentermine Abuse" an Age-old Concern with New Challenges: Review of Literature with Case Series". Annals of Indian Psychiatry. 7 (3): 262–266. doi: 10.4103/aip.aip_59_23 . ISSN   2588-8366.
  5. 1 2 3 4 5 6 7 8 9 10 Oliveira MF, Sousa HF, Lima MC, Oliveira JR (March 2011). "Mephentermine: rediscovering its biology and use, misuse and their implications". Braz J Psychiatry. 33 (1): 98–99. doi: 10.1590/s1516-44462011000100019 . PMID   21537728.
  6. 1 2 3 4 Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". Br J Pharmacol. 154 (3): 606–622. doi:10.1038/bjp.2008.124. PMC   2439527 . PMID   18500382.
  7. 1 2 3 4 5 6 7 8 9 10 Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 757. ISBN   978-3-88763-101-7 . Retrieved 28 July 2024.
  8. 1 2 3 4 5 6 "Mephentermine". drugs.com. 5 August 2020. Archived from the original on 5 August 2020. Retrieved 28 July 2024.
  9. 1 2 3 4 5 "Mephentermine". PubChem. Retrieved 28 July 2024.
  10. 1 2 Brofman BL, Hellerstein HK, Caskey WH (September 1952). "Mephentermine: an effective pressor amine; clinical and laboratory observations". Am Heart J. 44 (3): 396–406. doi:10.1016/0002-8703(52)90261-5. PMID   14952463.
  11. 1 2 3 Singh S, Gupta A, Sarkar S (2017). "Mephentermine Dependence in a Young Athlete: Case Report With Review of Literature". J Addict Med. 11 (4): 328–330. doi:10.1097/ADM.0000000000000313. PMID   28574863.
  12. ↑ Hsu MC, Lin SF, Kuan CP, Chu WL, Chan KH, Chang-Chien GP (March 2009). "Oxethazaine as the source of mephentermine and phentermine in athlete's urine". Forensic Sci Int. 185 (1–3): e1–5. doi:10.1016/j.forsciint.2008.12.009. PMID   19157735.
  13. ↑ Huang WH, Liu CH, Liu RH, Tseng YL (March 2010). "Confirming urinary excretion of mephentermine and phentermine following the ingestion of oxethazaine by gas chromatography-mass spectrometry analysis". J Anal Toxicol. 34 (2): 73–77. doi:10.1093/jat/34.2.73. PMID   20223098.
  14. ↑ William F Bruce, Szabo Joseph Lester, Tubis Samuel, U.S. patent 2,597,445 (1952 to Wyeth Corp)
  15. ↑ Zenitz BL, Macks EB, Moore ML (1948). "Preparation of α,α-Dimethyl- and N,α,α-Trimethyl-β-cyclohexylethylamine". Journal of the American Chemical Society. 70 (3): 955–957. doi:10.1021/ja01183a019.
  16. ↑ Angrist BM, Schweitzer JW, Gershon S, Friedhoff AJ (March 1970). "Mephentermine psychosis: misuse of the Wyamine inhaler". Am J Psychiatry. 126 (9): 1315–1317. doi:10.1176/ajp.126.9.1315. PMID   5413209.
  17. ↑ Uday GJ, Josh UG, Bhat SM (January 1988). "Mephentermine dependence with psychosis. A case report". Br J Psychiatry. 152: 129–131. doi:10.1192/bjp.152.1.129. PMID   3167321.
  18. ↑ Mendhekar DN, Sharma H, Dali JS (April 1999). "Case report of substance dependence with buprenorphine and mephentermine". Indian J Psychiatry. 41 (2): 160–162. PMC   2962841 . PMID   21455380.
  19. ↑ de Sousa HF, de Oliveira MF, da Costa Lima MD, de Oliveira JR (June 2010). "Mephentermine dependence without psychosis: a Brazilian case report". Addiction. 105 (6): 1129–1130. doi:10.1111/j.1360-0443.2010.02935.x. PMID   20456293.
  20. ↑ Kumar Mattoo S, Parakh P (June 2012). "Mephentermine dependence: an emerging challenge". CNS Neurosci Ther. 18 (6): 509–510. doi:10.1111/j.1755-5949.2012.00328.x. PMC   6493632 . PMID   22672305.
  21. ↑ Gehlawat P, Singh P, Gupta R, Arya S (2013). "Mephentermine dependence with psychosis". Gen Hosp Psychiatry. 35 (6): 681.e9–10. doi:10.1016/j.genhosppsych.2013.04.019. PMID   23759255.
  22. ↑ Gowda GS, Singh A, Ravi M, Math SB (October 2015). "Mephentermine dependence syndrome - A new emerging trend of substance use". Asian J Psychiatr. 17: 101–102. doi:10.1016/j.ajp.2015.07.006. PMID   26236018.
  23. ↑ Somani A (November 2020). "Mephentermine dependence in a young Indian adult without psychosis". BMJ Case Rep. 13 (11): e236924. doi:10.1136/bcr-2020-236924. PMC   7607562 . PMID   33139366.
  24. ↑ Roy P, Shah B, Karia S, Desousa A, Shah N (2021). "Mephentermine abuse - A case report". Indian J Psychiatry. 63 (4): 400–401. doi: 10.4103/psychiatry.IndianJPsychiatry_934_20 . PMC   8363899 . PMID   34456355.
  25. ↑ Singal AK, Deepti S, Sharma G, Kothari SS (February 2021). "Herculean mistake: mephentermine associated cardiomyopathy". Phys Sportsmed. 49 (1): 116–122. doi:10.1080/00913847.2020.1763146. PMID   32404042.
  26. 1 2 Bhardwaj A, Yadav J, Arya S, Gupta R (2022). "Mephentermine Misuse: An Impending Crisis among Sportspersons". J Psychoactive Drugs. 54 (2): 196–198. doi:10.1080/02791072.2021.1936701. PMID   34126873.
  27. ↑ "The Prohibited List". World Anti Doping Agency. 1 January 2024. Retrieved 28 July 2024.
  28. ↑ Goldberg LI (August 1968). "Use of sympathomimetic amines in heart failure". Am J Cardiol. 22 (2): 177–182. doi:10.1016/0002-9149(68)90223-3. PMID   4874959.
  29. ↑ Frye RL, Kahler RL, Braunwald E (September 1961). "The ineffectiveness of an inotropic agent, mephentermine (Wyamine), in the treatment of congestive heart failure". Am Heart J. 62 (3): 301–303. doi:10.1016/0002-8703(61)90395-7. PMID   13702337.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.