Amino Acids

Alanine

Physical And Pharmaceutical Properties
Name Status:USAN, rINN
Synonyms: A;Ala;Alaniini;Alanin;Alanina;Alaninas;L-Alanine;Alaninum;NSC-206315
Chemical Name: L-2-Aminopropionic acid
Molecular Formula: C3H7NO2
Molecular Weight:89.09
CAS Registry: 56-41-7
Pharmacopoeias:In Chin., Eur. (see About Martindale), and US.
Ph. Eur. 6.4 (Alanine). A white or almost white crystalline powder or colourless crystals. Freely soluble in water; very slightly soluble in alcohol. Protect from light.
USP 32 (Alanine). White, odourless, crystals or crystalline powder. Freely soluble in water; slightly soluble in 80% alcohol; insoluble in ether. pH of a 5% solution in water is between 5.5 and 7.0. Store in airtight containers.

Proprietary Names
Abufene (Bouchara, Singapore) ,Abufene (Bouchara-Recordati, Fr.) ,Amino MS (Larkhall Laboratories, UK) ,Chetonex (Humana, Ital.) ,Normoprost Compuesto (Temis, Arg.) ,Tebetane Composto (Ferraz, Lynce, Port.) ,Tebetane Compuesto (ProStrakan, Spain)

Profile
Alanine is an aliphatic non-essential amino acid. It is used as a dietary supplement. The dipeptide N(2)-L-alanyl-L-glutamine is used similarly.
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Hypoglycaemia
References to the investigational use of alanine in the management of insulin-induced hypoglycaemia.1-4
1. Wiethop BV, Cryer PE. Glycemic actions of alanine and terbutaline in IDDM. Diabetes Care 1993; 16: 1124-30. (PubMed id:8375242)
2. Wiethop BV, Cryer PE. Alanine and terbutaline in treatment of hypoglycemia in IDDM. Diabetes Care 1993; 16: 1131-6. (PubMed id:8375243)
3. Saleh TY, Cryer PE. Alanine and terbutaline in the prevention of nocturnal hypoglycemia in IDDM. Diabetes Care 1997; 20: 1231-6. (PubMed id:9250445)
4. Evans ML, et al. Alanine infusion during hypoglycaemia partly supports cognitive performance in healthy human subjects. Diabet Med 2004; 21: 440-6. (PubMed id:15089788)

Arginine

Physical And Pharmaceutical Properties
Name Status:rINN
Synonyms: Arg;Arginiini;Arginin;Arginina;Argininas;L-Arginine;Argininum;R
Chemical Name: L-2-Amino-5-guanidinovaleric acid
Molecular Formula: C6H14N4O2
Molecular Weight:174.2
CAS Registry: 74-79-3
Notes and Warnings: Arginine may be restricted in certain sports, as it is considered to be a member of a prohibited group (? S2-2; Growth hormone releasing factors); competitors should check with the appropriate sports authorities.
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Arginine). A white or almost white crystalline powder, or colourless crystals. Freely soluble in water; very slightly soluble in alcohol. Protect from light.
USP 32 (Arginine). White, practically odourless crystals. Freely soluble in water; sparingly soluble in alcohol; insoluble in ether.

Proprietary Names
Acrea (Aulo Gelio, Arg.) ,Anti-Flab (Suisse, Austral.) ,Arginine Capsules USP 32,Arginine Tablets USP 32,Arginitric (Innopharm, Malaysia) ,Bioarginina (Damor, Ital.) ,Biofertil M (Casen Fisons, Spain) ,Brugesic Plus (Elmor, Venez.) ,Calciofix (Damor, Ital.) ,Carginine (Coraltis, Israel) ,Dinavital C (Merck, Braz.) ,Fertibion (Tegur, Mex.) ,Hepagrume (EG, Fr.) ,Hepalersa Compuesto (Lersa, Spain) ,Hepasteril (Fresenius, Ger.) ,Hepasteril A (Fresenius, Ger.) ,Infumal (Serum-Werk Bernburg, Ger.) ,Isoram (Bieffe, Ital.) ,Leberinfusion (Fresenius Kabi, Austria) ,Linfoiodine (Noos, Ital.) ,Liporex (Synthelabo, Fr.) ,Necroplex (Heralds, Braz.) ,Ornihepat (Faria, Braz.) ,Ornitargin (Baldacci, Braz.) ,Rocmalat (Strathmann, Hung.) ,Rocmalat (Stroschein, Ger.) ,Rocmalat F (Hek, Ger.) ,Rocmalat L (Hek, Ger.) ,Rocmaline (Aerocid, Fr.) ,Rocmaline (Fresenius Kabi, Austria) ,Rocmaline Desodee (Roques, Fr.) ,Sanieb (Puerto Galiano, Spain) ,Sirec (Ethica, Indon.) ,Somatron (Volchem, Ital.) ,Spermargin (Isnardi, Ital.) ,Sterofundin CH (Braun, Ger.) ,Sterofundin CH compositum (Braun, Ger.) ,Ureadin 30 (Isdin, Chile) ,Viridex (Transpharma, Fr.)

Arginine Aspartate

Physical And Pharmaceutical Properties
Synonyms: Arginiiniaspartaatti;Arginina, aspartato de;Argininaspartat;Arginin-aspartát;Arginine, aspartate d’;Arginini aspartas;Arginino aspartatas;Aspargininum
Chemical Name: (2S)-2-Amino-5-guanidinopentanoic acid (2S)-2-aminobutanedioate
Molecular Formula: C10H21N5O6
Molecular Weight:307.3
CAS Registry: 7675-83-4
Notes and Warnings: Arginine Aspartate may be restricted in certain sports, as it is considered to be a member of a prohibited group (? S2-2; Growth hormone releasing factors); competitors should check with the appropriate sports authorities.
Pharmacopoeias:In Eur. (see About Martindale).
Ph. Eur. 6.4 (Arginine Aspartate). White or almost white granules or powder. Very soluble in water, practically insoluble in alcohol and in dichloromethane.

Proprietary Names
Activital Forte (Welti, Switz.) ,Asparten (Grunenthal, Port.) ,Bio-Energol Plus (Yabrofarma, Port.) ,Desfatigan (IMA, Braz.) ,Dynamisan (Novartis Consumer, Switz.) ,Dynamisan (Wander, Belg.) ,Dynamogen (Faes, Spain) ,Eubiol (Chephasaar, Ger.) ,Fastenyl (Viatris, Fr.) ,Glutargin (Terapeutico, Ital.) ,Laclorene (Spedrog, Arg.) ,Pan-Astenico R (Vitoria, Port.) ,Pargine (Meda, Fr.) ,Potenciator (Iquinosa, Spain) ,Reforgan (Nikkho, Braz.) ,Sangenor (Mundipharma, Austria) ,Sargenor (Meda, Ital.) ,Sargenor (Meda, Port.) ,Sargenor (Viatris, Fr.) ,Sargenor (Viatris, Spain) ,Sargenor a la Vitamine C (Viatris, Fr.) ,Sargisthene (Meda, Spain) ,Sorbenor (Casen Fleet, Spain) ,Targifor (Sanofi-Aventis, Braz.) ,Targifor C (Sanofi-Aventis, Braz.)

Arginine Glutamate

Physical And Pharmaceutical Properties
Name Status:BAN, USAN, rINNM
Synonyms: Arginina, glutamato de;Arginine, Glutamate d’;Arginini Glutamas;Glutamato de arginina
Chemical Name: L-Arginine L-glutamate
Molecular Formula: C6H14N4O2,C5H9NO4
Molecular Weight:321.3
CAS Registry: 4320-30-3
Notes and Warnings: Arginine Glutamate may be restricted in certain sports, as it is considered to be a member of a prohibited group (? S2-2; Growth hormone releasing factors); competitors should check with the appropriate sports authorities.
ATC:A05BA01

Proprietary Names
Dynamisan (Mipharm, Ital.) ,Dynamisan (Novartis Consumer, Port.) ,Dynamisan (Novartis Sante, Fr.) ,Energitum (Zambon, Fr.) ,Glutargin (Terapeutico, Ital.)

Arginine Hydrochloride

Physical And Pharmaceutical Properties
Name Status:USAN, rINNM
Synonyms: Arginiinihydrokloridi;Arginina, hidrocloruro de;Arginine, chlorhydrate d’;L-Arginine Monohydrochloride;Arginin-hidroklorid;Arginin-hydrochlorid;Argininhydroklorid;Arginini hydrochloridum;Arginino hidrochloridas;Hidrocloruro de arginina
Molecular Formula: C6H14N4O2,HCl
Molecular Weight:210.7
CAS Registry: 1119-34-2
Notes and Warnings: Arginine Hydrochloride may be restricted in certain sports, as it is considered to be a member of a prohibited group (? S2-2; Growth hormone releasing factors); competitors should check with the appropriate sports authorities.
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Arginine Hydrochloride). A white or almost white crystalline powder, or colourless crystals. Freely soluble in water; very slightly soluble in alcohol. Protect from light.
USP 32 (Arginine Hydrochloride). White, practically odourless, crystals or crystalline powder. Freely soluble in water.
ATC:B05XB01

Proprietary Names
Arginine Capsules USP 32,Arginine Hydrochloride Injection USP 32,Arginine Hydrochloride Intravenous Infusion BP 2009,Arginine Tablets USP 32,Arginotri-B (Bouchara, Switz.) ,Arginotri-B (Bouchara-Recordati, Fr.) ,Arnilose (AJC, Fr.) ,Bioarginina (Damor, Ital.) ,Citruplexina (Synthelabo, Ital.) ,Epuram (Pharmafarm, Fr.) ,Glutarsin E (Berlin-Chemie, Ger.) ,Glutarsin E (Berlin-Chemie, Hung.) ,Hepargitol (Elerte, Fr.) ,Ipoazotal (SIT, Ital.) ,Ipoazotal Complex (SIT, Ital.) ,Polilevo (Monsanto, Ital.) ,Polilevo (Spitzner, Ger.) ,Polilevo N (Taurus, Ger.) ,R-Gene (Kabivitrum, USA) ,Rocmalat (Stroschein, Ger.) ,Sargenor Plus (Meda, Ital.) ,Vitasprint Complex (Balverda, Ital.) ,Vitasprint Complex (Whitehall-Robins, Switz.)

Adverse Effects and Precautions

Extravasation. Hyperkalaemia. Hypersensitivity.

Myocardial infarction.
Nausea, vomiting, flushing, headache, numbness, and local venous irritation may occur if arginine solutions are infused too rapidly. Elevated plasma-potassium concentrations have been reported in uraemic patients and arginine should therefore be used with caution in patients with renal disease or anuria. Arginine hydrochloride should be given cautiously to patients with electrolyte disturbances as its high chloride content could lead to the development of hyperchloraemic acidosis.

Extravasation
Full-thickness skin necrosis has been reported1,2 after extravasation of a 10% solution of arginine hydrochloride. Both osmotic and local hyperkalaemic effects have been proposed as a mechanism for the injury.1
1. Bowlby HA, Elanjian SI. Necrosis caused by extravasation of arginine hydrochloride. Ann Pharmacother 1992; 26: 263-4. (PubMed id:1554945)
2. Salameh Y, Shoufani A. Full-thickness skin necrosis after arginine extravasation–a case report and review of literature. J Pediatr Surg 2004; 39: E9-E11. (PubMed id:15065075)

Hyperkalaemia
Two alcoholic patients with severe liver disease and moderate renal insufficiency developed severe hyperkalaemia when given arginine hydrochloride and one died.1 Both patients had received a total of 300 mg of spironolactone some time before arginine hydrochloride, but the contribution of spironolactone to the hyperkalaemia was not known. In a study to investigate the mechanism of metabolic changes due to arginine, plasma-potassium concentrations were found to be significantly higher in diabetic subjects than those for normal subjects, leading the authors to suppose that while arginine-induced hyperkalaemia may be promoted by low insulin blood levels, it could not be attributed to glucagon, pH changes, or aldosterone inhibition.2
In another fatal case due to an overdose of arginine,3 a 21-month-old girl developed an acute metabolic acidosis with transient but severe hyponatraemia, and irreversible brain death; no hyperkalaemia was observed. Unlike the previously reported case, the patient had normal renal function, and the authors supposed the absence of hyperkalaemia to be due to a rapid increase in renal potassium excretion.
1. Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med 1978; 89: 632-4. (PubMed id:717931)
2. Massara F, et al. The risk of pronounced hyperkalaemia after arginine infusion in the diabetic subject. Diabete Metab 1981; 7: 149-53. (PubMed id:7319114)
3. Gerard JM, Luisiri A. A fatal overdose of arginine hydrochloride. J Toxicol Clin Toxicol 1997; 35: 621-5. (PubMed id:9365430)

Hypersensitivity.
There are 2 reports of anaphylactic reactions shortly after the start of infusions of arginine 5 or 10% given to test growth-hormone output.1,2 Anaphylaxis to arginine was considered to be a very rare event and only one other apparent allergic reaction had been reported to the manufacturers.
1. Tiwary CM, et al. Anaphylactic reaction to arginine infusion. N Engl J Med 1973; 288: 218. (PubMed id:4682241)
2. Resnick DJ, et al. Case report of an anaphylactoid reaction to arginine. Ann Allergy Asthma Immunol 2002; 88: 67-8. (PubMed id:11814282)

Myocardial infarction.
A placebo-controlled trial investigated whether the addition of arginine to standard therapy after myocardial infarction would decrease vascular stiffness and improve left ventricular function. The study was stopped early due to an increased number of deaths in the arginine group. The authors commented that, while the results could be due to chance, nevertheless arginine should not be given to patients after a myocardial infarction.1
1. Schulman SP, et al. L-Arginine therapy in acute myocardial infarction: the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA 2006; 295: 58-64. (PubMed id:16391217)

Uses and Administration

Hyperammonaemia. Hypotensive action.

Necrotising enterocolitis.
Arginine is a basic amino acid that is essential for infant growth. It is used as a dietary supplement.
Arginine stimulates the release of growth hormone by the pituitary gland and may be used instead of, or in addition to, other tests such as insulin-induced hypoglycaemia, for the evaluation of growth disorders; false-positive and false-negative results are relatively common and evaluation therefore should not be made on the basis of a single arginine test. It is used as a 10% solution of the hydrochloride in usual doses of 30 g by intravenous infusion given over 30 minutes; children should be given 500 mg/kg.
Arginine is used in certain conditions accompanied by hyperammonaemia; for further details see Arginine Hydrochloride.
Arginine hydrochloride has also been used as an acidifying agent. In severe metabolic alkalosis intravenous doses have been calculated by the formula:
intravenous dose (in grams) =
desired decrease in plasma-bicarbonate concentration
(mEq or mmol/litre)
x
[patient’s body-weight (in kg)/9.6]
In forced acid diuresis to hasten drug elimination after overdose a suggested dose has been 10 g intravenously over 30 minutes. However, this has the potential to cause myoglobinuria with acute renal failure, and is rarely used.
Arginine may also be used in the form of the acetylasparaginate, aspartate, citrate, glutamate, oxoglurate, tidiacicate (thiazolidine-2,4-dicarboxylate), and timonacicate (thiazolidine-4-carboxylate). Formulation as an arginine salt is used to improve the solubility of a number of drugs, notably analgesics and antibacterials.

References
1. Tapiero H, et al. Arginine. Biomed Pharmacother 2002; 56: 439-45. (PubMed id:12481980)
2. Tong BC, Barbul A. Cellular and physiological effects of arginine. Mini Rev Med Chem 2004; 4: 823-32. (PubMed id:15544543)

Hyperammonaemia
Hyperammonaemia is a characteristic feature of inborn errors of the urea cycle, caused by defects in the enzymes carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase (causing hyperargininaemia), or N-acetylglutamate synthase (NAGS).1,2 During the urea cycle, waste ammonia, in the form of the ammonium ion, is normally condensed with bicarbonate and ATP to form carbamoyl phosphate which undergoes several more reactions, including one leading to the synthesis of arginine, and ultimate transformation to urea for excretion. Thus, in defects of this cycle ammonia accumulates and arginine synthesis is deficient.3 Hyperammonaemia is most severe when the enzyme defect occurs in the early steps of the urea cycle, such as in CPS or OTC deficiency, and is less severe at later stages, as in ASL or arginase deficiency.2 Hyperammonaemia is often associated with respiratory alkalosis in patients with urea cycle disorders.3
The basis of treatment is dietary protein restriction, to decrease the requirement for waste nitrogen synthesis,4 and the use of drugs to stimulate alternative pathways of waste nitrogen excretion.5,6 These include arginine, citrulline, sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate. In the initial management of severe hyperammonaemia, haemodialysis is preferred over peritoneal dialysis because it is more effective.3,7
Arginine supplements are given except in hyperargininaemia.5,7 Citrulline may be used in some cases instead;8 it may be useful for CPS and OTC deficiency (in doses of about 170 mg/kg daily or 3.8 g/m2 daily),5,6,9 but it is not recommended for patients with ASS or ASL deficiency, as levels of citrulline are already elevated.5,10 Some recommend citrulline with arginine in acute hyperammonaemia to aid additional removal of nitrogen.9 For the treatment of acute hyperammonaemia, some recommend a loading dose of arginine 600 mg/kg over 90 minutes pending definitive diagnosis.3,10 Alternatively, a loading dose of 200 mg/kg or 4 g/m2 has been advocated for CPS or OTC deficiency,6,9,10 and 600 mg/kg or 12 g/m2 for ASS or ASL deficiency.6,9,10 The same dose as the loading dose is then given over 24 hours, as a constant maintenance infusion,6,9,10 until conversion to oral medication is made.10 For long-term management of ASS or ASL deficiency, doses of arginine ranging from 400 to 700 mg/kg daily have been recommended.5,6,9,10
Patients also receive treatment with sodium benzoate and sodium phenylacetate6,10 or sodium phenylbutyrate.5,6 ASL deficiency can be managed with protein restriction and arginine alone,6,11 although some still advocate the use of sodium phenylbutyrate.5,8 When sodium benzoate is conjugated with glycine and excreted as hippuric acid it provides an alternative pathway of nitrogen excretion, while sodium phenylacetate and sodium phenylbutyrate provide a second and even more effective pathway by conjugation with glutamine.6,7,10 Some consider intravenous sodium benzoate and sodium phenylacetate the treatment of choice in acute hyperammonaemia; sodium phenylbutyrate is recommended for chronic management.9 In a 25-year, open-label, uncontrolled study, intravenous therapy with sodium phenylacetate and sodium benzoate clearly improved survival in patients with acute hyperammonaemia, with an overall survival rate of 84%; survival was also related to peak plasma ammonium concentration and age. Haemodialysis was also used to control hyperammonaemia, especially in neonates and older patients who were less responsive to intravenous therapy.12
It has been suggested that carnitine supplementation (at 100 mg/kg daily9 either orally or intravenously) should be added to minimise neurological symptoms and toxicity, but its value is uncertain.4,13 Low carnitine levels have been reported to be uncommon in patients with urea cycle disorders and, in patients treated with sodium benzoate, benzoyl carnitine may form, negating any potential benefit from carnitine supplementation.8
Liver transplantation (Immunosuppressants) may achieve long-term correction of urea cycle disorders, even in the very young patient, and gene replacement therapy is under investigation.14
Hyperammonaemia and hepatic encephalopathy (Gastrointestinal Drugs) can also arise from other causes7,13 for which arginine may not be advocated. Carglumic acid (Carglumic Acid) is the treatment of choice for patients with hyperammonaemia arising from NAGS deficiency.
For further information on the agents mentioned above, see
Arginine, Arginine Hydrochloride
Carnitine, Levocarnitine Propionate Hydrochloride
Citrulline, Citrulline
Sodium Benzoate, Sodium Benzoate
Sodium Phenylacetate, Sodium Phenylacetate
Sodium Phenylbutyrate, Sodium Phenylbutyrate
1. Summar M, Tuchman M. Proceedings of a consensus conference for the management of patients with urea cycle disorders. J Pediatr 2001; 138 (suppl): S6-S10. (PubMed id:11148544)
2. Shih VE. Alternative-pathway therapy for hyperammonemia. N Engl J Med 2007; 356: 2321-2. (PubMed id:17538092)
3. The Urea Cycle Disorders Conference Group. Consensus statement from a conference for the management of patients with urea cycle disorders. J Pediatr 2001; 138 (suppl): S1-S5. (PubMed id:11148543)
4. Leonard JV. The nutritional management of urea cycle disorders. J Pediatr 2001; 138 (suppl): S40-S45. (PubMed id:11148548)
5. Berry GT, Steiner RD. Long-term management of patients with urea cycle disorders. J Pediatr 2001; 138 (suppl): S56-S61. (PubMed id:11148550)
6. Batshaw ML, et al. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 2001; 138 (suppl): S46-S55. (PubMed id:11148549)
7. Leonard JV, Morris AAM. Urea cycle disorders. Semin Neonatol 2002; 7: 27-35. (PubMed id:12069536)
8. Wilcken B. Problems in the management of urea cycle disorders. Mol Genet Metab 2004; 81 (suppl): S86-S91. (PubMed id:15050980)
9. Kleppe S, et al. Urea cycle disorders. Curr Treat Options Neurol 2003; 5: 309-19. (PubMed id:12791198)
10. Summar M. Current strategies for the management of neonatal urea cycle disorders. J Pediatr 2001; 138 (suppl): S30-S39. (PubMed id:11148547)
11. Brusilow SW, et al. Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis. N Engl J Med 1984; 310: 1630-4. (PubMed id:6427608)
12. Enns GM, et al. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders. N Engl J Med 2007; 356: 2282-92. (PubMed id:17538087)
13. Leonard JV, Morris AAM. Inborn errors of metabolism around time of birth. Lancet 2000; 356: 583-7. (PubMed id:10950248)
14. Lee B, Goss J. Long-term correction of urea cycle disorders. J Pediatr 2001; 138 (suppl): S62-S71. (PubMed id:11148551)
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Hypotensive action.
Arginine is the physiological precursor of nitric oxide and this has been suggested as an explanation for the hypotensive effect that has been reported in healthy subjects1-3 and hypertensive patients1,4 given infusions of arginine, although effects unrelated to nitric oxide generation cannot be excluded.4
Oral arginine has also been reported to significantly decrease mean systolic blood pressure in hypertensive patients,5 in patients on haemodialysis, and in renal transplant recipients.6 In patients with essential hypertension, a single dose of arginine by mouth had no effect on blood pressure, although it did improve endothelium-dependent flow-mediated dilatation of the brachial artery compared with placebo.7 In patients with pulmonary hypertension, short-term use of arginine has reduced pulmonary arterial pressure.8-10
In pregnant women with pre-eclampsia (see Hypertension, Cardiovascular Drugs), plasma-arginine concentrations were found to be markedly reduced compared with control subjects.11 Arginine infusions of 20 g, given to women with mild to moderate gestational hypertension,12 and 30 g given to pre-eclamptic women,13 significantly reduced systolic and diastolic blood pressure, with no adverse effect on fetal heart rate in the one study.12 In a study of pre-eclamptic women given arginine 12 g daily for 2 days by mouth, no significant differences in diastolic blood pressure were seen compared with those receiving placebo.14 However, in another study of pre-eclamptic women given 3 g arginine daily for 3 weeks, systolic, diastolic and mean arterial pressure were significantly reduced compared with those taking placebo.15
Because of apparent improvement in endothelial function with arginine, some interest has surrounded its potential role in other cardiovascular diseases, such as coronary artery disease and heart failure.16 Decrease in plasma-cholesterol concentrations has also been reported in 2 hypercholesterolaemic patients given arginine infusions.17 However, long-term supplementation was found not to be helpful (and possibly harmful) in patients with peripheral arterial disease,18 and arginine therapy has been implicated in increased mortality when given to patients after myocardial infarction (see under Adverse Effects and Precautions, Arginine Hydrochloride).
1. Nakaki T, et al. L-arginine-induced hypotension. Lancet 1990; 336: 696. (PubMed id:1975886)
2. Hishikawa K, et al. L-arginine-induced hypotension. Lancet 1991; 337: 683-4. (PubMed id:1672031)
3. Petros AJ, et al. L-arginine-induced hypotension. Lancet 1991; 337: 1044-5. (PubMed id:1673199)
4. Pedrinelli R, et al. Pressor, renal and endocrine effects of L-arginine in essential hypertensives. Eur J Clin Pharmacol 1995; 48: 195-201. (PubMed id:7589041)
5. Palloshi A, et al. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol 2004; 93: 933-5. (PubMed id:15050504)
6. Kelly BS, et al. Oral arginine improves blood pressure in renal transplant and hemodialysis patients. J Parenter Enteral Nutr 2001; 25: 194-202. (PubMed id:11434650)
7. Lekakis JP, et al. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol 2002; 86: 317-23. (PubMed id:12419572)
8. Mehta S, et al. Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 1995; 92: 1539-45. (PubMed id:7664438)
9. Nagaya N, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001; 163: 887-91. (PubMed id:11282761)
10. Morris CR, et al. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med 2003; 168: 63-9. (PubMed id:12626350)
11. D’Aniello G, et al. Plasma L-arginine is markedly reduced in pregnant women affected by preeclampsia. J Chromatogr B Biomed Sci Appl 2001; 753: 427-31. (PubMed id:11334360)
12. Neri I, et al. Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women. J Matern Fetal Neonatal Med 2004; 16: 23-6. (PubMed id:15370078)
13. Facchinetti F, et al. L-Arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release. J Soc Gynecol Investig 1999; 6: 202-7. (PubMed id:10486782)
14. Staff AC, et al. Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand 2004; 83: 103-7. (PubMed id:14678093)
15. Rytlewski K, et al. Effects of prolonged oral supplementation with L-arginine on blood pressure and nitric oxide synthesis in preeclampsia. Eur J Clin Invest 2005; 35: 32-7. (PubMed id:15638817)
16. Cheng JWM, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001; 35: 755-64. (PubMed id:11408995)
17. Korbut R, et al. Effect of L-arginine on plasminogen-activator inhibitor in hypertensive patients with hypercholesterolemia. N Engl J Med 1993; 328: 287-8. (PubMed id:8418418)
18. Wilson AM, et al. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 2007; 116: 188-95. (PubMed id:17592080)
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Necrotising enterocolitis.
A systematic review1 considered that although there was evidence suggesting that supplementation of the feed of premature neonates with arginine could prevent the development of necrotising enterocolitis (Antibacterials), it was insufficient to recommend the practice without further study.
1. Shah P, Shah V. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Available in The Cochrane Database of Systematic Reviews; Issue 3. Chichester: John Wiley; 2007 (accessed 24/06/08). (PubMed id:17636753)

Glycine

Physical And Pharmaceutical Properties
Name Status:rINN
Synonyms: Acidum Aminoaceticum;Aminoacetic Acid;Aminoättiksyra;Aminoetikkahappo;E640 (glycine or glycine sodium);G;Glicin;Glicina;Glicinas;Glicyna;Gly;Glycin;Glycinum;Glycocoll;Glysiini;Sucre de Gélatine
Molecular Formula: C2H5NO2
Molecular Weight:75.07
CAS Registry: 56-40-6
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Glycine). A white or almost white crystalline powder. It exhibits polymorphism. Freely soluble in water; very slightly soluble in alcohol. A 5% solution in water has a pH of 5.9 to 6.4.
USP 32 (Glycine). A white, odourless crystalline powder. Soluble 1 in 4 of water at 25°, 1 in 2.6 at 50°, 1 in 1.9 at 75°, and 1 in 1.5 at 100°; soluble 1 in 1254 of alcohol; very slightly soluble in ether. Its solutions are acid to litmus.
ATC:B05CX03

Proprietary Names
Actilevol C (Wasserman, Spain) ,Alka-Prim (Polpharma, Pol.) ,Aspiglicina (Antonetto, Ital.) ,Asprocol (ICN, Pol.) ,Beechams Lemon Tablets (SmithKline Beecham Consumer, UK) ,B-Vesil (Daudt, Braz.) ,Cal Alkyline (Eagle, Austral.) ,Calglycine Antacid (Rugby, USA) ,Caparin (Osotspa, Thai.) ,Cardiprin (Reckitt Benckiser, Austral.) ,Cardiprin (Reckitt Benckiser, Hong Kong) ,Cardiprin (Reckitt Benckiser, Malaysia) ,Cardiprin (Reckitt Benckiser, NZ) ,Cardiprin (Reckitt Benckiser, Singapore) ,Cardiprin (Reckitt Benckiser, Thai.) ,Centramin (Rosch & Handel, Austria) ,Contrexyn (Supra Ferbindo, Indon.) ,Cotaryl (FDC, India) ,Cristopal (Alcon, Fr.) ,DAM Antacidum (Corifel, Switz.) ,Derm’Intim (Ducray, Fr.) ,Derm Hydralin (Bayer, Fr.) ,Detoxicon (Schering, Ital.) ,Detoxicon (SIT, Ital.) ,Digest-eze (Medinat, Austral.) ,Digestivo Antonetto (Antonetto, Ital.) ,Disprin Direct (Reckitt Benckiser, Austral.) ,Dolotol 12 (Saval, Chile) ,Dulcipirina (SmithKline Beecham, Spain) ,Eltacin (Biotiki, Rus.) ,Estomil (Salvat, Spain) ,Exepin Cortex (SmithKline Beecham, Ital.) ,Geyfritz (Geymonat, Ital.) ,Glisuret (Pisa, Mex.) ,Glycine Irrigation Solution BP 2009,Glycine Irrigation USP 32,Glyprin (CCM, Hong Kong) ,Glyprin (CCM, Malaysia) ,Glyprin (Upha, Singapore) ,Godamed (Pfleger, Ger.) ,Godasal (Pfleger, Cz.) ,Gyn-Hydralin (Bayer, Fr.) ,Gyn-Hydralin (Roche Nicholas, Hong Kong) ,Inzana (Konimex, Indon.) ,Item Alphazole (Gandhour, Fr.) ,Juvepirine (Asta Medica, Fr.) ,Lysoprin (Rafa, Israel) ,Minigrip (Kalbe, Indon.) ,Nevrostenina B12 (Formenti, Ital.) ,Normoprost Compuesto (Temis, Arg.) ,Pansan (Kali-Chemie, Ger.) ,Panzynorm forte (Nordmark, Ger.) ,Paynocil (Beecham Research, UK) ,Phakan (Chauvin, Fr.) ,Phakan (Chauvin, Port.) ,Phakolen (Bausch & Lomb, Switz.) ,Praecineural (Pfleger, Ger.) ,Proacid (Procare, Austral.) ,Pruriced (Uriage, Fr.) ,Regla pH (UCB, Switz.) ,Robusanon (Robugen, Ger.) ,Sanieb (Puerto Galiano, Spain) ,Sargepirine (Asta Medica, Fr.) ,Segel (Diba, Mex.) ,Slimswift Night Trim (Cantassium Co., UK) ,Solvin (Reckitt & Colman, Austral.) ,Tebetane Composto (Ferraz, Lynce, Port.) ,Tebetane Compuesto (ProStrakan, Spain) ,Tonitensyl (Bailly, Fr.) ,Ulsade (Cambridge, Austral.) ,Uro 3000 (Aguettant, Fr.)

Adverse Effects and Precautions
Systemic absorption of glycine irrigation solutions can lead to disturbances of fluid and electrolyte balance and cardiovascular and pulmonary disorders (see Glycine).
Glycine irrigation should be used cautiously in patients with hepatic impairment since any absorption and consequent metabolism may cause hyperammonaemia. The possible effects on fluid and electrolyte balance warrant cautious use in patients with cardiopulmonary or renal dysfunction; glycine irrigation is contra-indicated in anuric patients.

Systemic absorption
Absorption of glycine irrigation solution during surgical procedures can cause disturbances of the circulatory and nervous systems.1-3 Often seen after transurethral resection of the prostate, these symptoms and signs have been referred to as the transurethral resection syndrome,1 although they have also been described after other urological or gynaecological surgical procedures.4,5 Hyponatraemia and glycine toxicity are thought to be responsible for the clinical manifestations.1,2,5
Symptoms and signs include chest pains, hypertension, hypotension, bradycardia, anuria, dyspnoea, nausea, vomiting, restlessness, confusion, apprehension, irritability, headache, and seizures.1,3-5 Chills, diarrhoea, and abdominal pain have also been reported,1 as have visual disturbances and blindness.3,6 Myocardial infarction,7,8 coma, and death may occur.5,7
Absorption may occur rapidly, through the intravascular route, or, more rarely, slowly via extravascular absorption.1,2,4 Extravasation should be suspected when abdominal pain and swelling are apparent.4,9 Ethanol has been added to the irrigation fluid, and ethanol breath tests performed regularly during procedures in order to detect and monitor absorption.1,2,4,9 However, the syndrome has still occurred despite monitoring;9 awareness of the pattern of ethanol changes and clinical symptoms associated with extravascular as well as intravascular absorption are considered essential.4,9
1. Olsson J, et al. Symptoms of the transurethral resection syndrome using glycine as the irrigant. J Urol (Baltimore) 1995; 154: 123-8. (PubMed id:7776407)
2. Tauzin-Fin P. Complication des liquides d’irrigation à base de glycocolle: le syndrome de résorption. Therapie 2002; 57: 48-54. (PubMed id:12090147)
3. Radziwill AJ, et al. Visual disturbances and transurethral resection of the prostate: the TURP syndrome. Eur Neurol 1997; 38: 7-9. (PubMed id:9252792)
4. Hahn RG. Transurethral resection syndrome after transurethral resection of bladder tumours. Can J Anaesth 1995; 42: 69-72. (PubMed id:7889587)
5. Siddiqui MA, et al. Glycine irrigant absorption syndrome following cystoscopy. Clin Nephrol 1996; 45: 365-6. (PubMed id:8738677)
6. Karci A, Erkin Y. Transient blindness following hysteroscopy. J Int Med Res 2003; 31: 152-5. (PubMed id:12760320)
7. Byard RW, et al. Glycine toxicity and unexpected intra-operative death. J Forensic Sci 2001; 46: 1244-6. (PubMed id:11569574)
8. Hahn RG, Persson P-G. Acute myocardial infarction after prostatectomy. Lancet 1996; 347: 335. (PubMed id:8569399)
9. Hahn RG. Life-threatening transurethral resection syndrome despite monitoring of fluid absorption with ethanol. Eur J Anaesthesiol 1995; 12: 431-3. (PubMed id:7588674)

Uses and Administration
Glycine is a non-essential aliphatic amino acid. It is used as a dietary supplement.
Glycine is sometimes used with antacids in the treatment of gastric hyperacidity. It is also used as an ingredient of some aspirin preparations with the object of reducing gastric irritation.
Sterile solutions of glycine 1.5% in water, which are hypotonic and non-conductive, are used as urogenital irrigation solutions during certain surgical procedures, particularly transurethral resection of the prostate.
Glycine hydrochloride has also been used.

Leucine

Physical And Pharmaceutical Properties
Name Status:USAN, rINN
Synonyms: α-Aminoisocaproic Acid;L;Leu;Leucin;Leucina;Leucinas;L-Leucine;Leucinum;Leucyna;Leusiini
Chemical Name: L-2-Amino-4-methylvaleric acid
Molecular Formula: C6H13NO2
Molecular Weight:131.2
CAS Registry: 61-90-5
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Leucine). A white or almost white, crystalline powder or shiny flakes. Sparingly soluble in water; practically insoluble in alcohol. It dissolves in dilute mineral acids and in dilute solutions of alkali hydroxides. Protect from light.
USP 32 (Leucine). White, practically odourless crystals. Sparingly soluble in water; insoluble in ether. pH of a 1% solution in water is between 5.5 and 7.0.

Proprietary Names
Bramin-hepa (Merz, Ger.) ,Falkamin (Abbott, Ital.) ,Falkamin (Falk, Ger.) ,Isobranch (Bieffe, Ital.) ,Isoram (Bieffe, Ital.) ,Lactostrict (Fresenius, Ger.) ,Revitalose (UCB, Fr.)

Profile
Leucine is a branched-chain aliphatic amino acid that is an essential constituent of the diet. It is used as a dietary supplement. It is also an ingredient of several preparations that have been promoted for disorders of the liver.

Lysine

Physical And Pharmaceutical Properties
Name Status:USAN, rINN
Synonyms: K;Lisina;Lys;L-Lysine;Lysinum
Chemical Name: L-2,6-Diaminohexanoic acid
Molecular Formula: C6H14N2O2
Molecular Weight:146.2
CAS Registry: 56-87-1
Pharmacopoeias:In Ger. as the monohydrate.
ATC:B05XB03

Proprietary Names
Ascorbamine (Pharmuka, Fr.) ,Calciofix (Damor, Ital.) ,Digezym (Quality, Hong Kong) ,Enisyl (Person & Covey, USA) ,Incremin (Wyeth Lederle, Port.) ,Labophylline (Laboratories for Applied Biology, UK) ,Latlas (Atlas, Arg.) ,Rinotrofina C (Farmila, Ital.) ,Vitaline (Bioglan, Austral.)

Lysine Acetate

Physical And Pharmaceutical Properties
Name Status:rINNM
Synonyms: Acetato de lisina;Lisina, acetato de;Lizino acetatas;Lizyny octan;Lys Acetate;Lysiiniasetaatti;Lysinacetat;Lysin-acetát;Lysine, acétate de;L-Lysine Monoacetate;Lysini acetas
Chemical Name: L-2,6-Diaminohexanoic acid acetate
Molecular Formula: C6H14N2O2,C2H4O2
Molecular Weight:206.2
CAS Registry: 57282-49-2
Pharmacopoeias:In Chin., Eur. (see About Martindale), and US.
Ph. Eur. 6.4 (Lysine Acetate). A white or almost white, crystalline powder or colourless crystals. It exhibits polymorphism. Freely soluble in water; very slightly soluble in alcohol. Protect from light.
USP 32 (Lysine Acetate). White, odourless crystals or crystalline powder. Freely soluble in water.

Lysine Hydrochloride

Physical And Pharmaceutical Properties
Name Status:USAN, rINNM
Synonyms: Hidrocloruro de lisina;Lisina, hidrocloruro de;Lizin-hidroklorid;Lizino hidrochloridas;Lys Hydrochloride;Lysiinihydrokloridi;Lysine, chlorhydrate de;L-Lysine Monohydrochloride;Lysin-hydrochlorid;Lysinhydroklorid;Lysini hydrochloridum
Chemical Name: L-2,6-Diaminohexanoic acid hydrochloride
Molecular Formula: C6H14N2O2,HCl
Molecular Weight:182.6
CAS Registry: 657-27-2
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Lysine Hydrochloride). A white or almost white, crystalline powder or colourless crystals. Freely soluble in water; slightly soluble in alcohol. Protect from light.
USP 32 (Lysine Hydrochloride). A white, odourless powder. Freely soluble in water.

Proprietary Names
Acti 5 (Pierre Fabre, Fr.) ,Acticinco (Robapharm, Spain) ,Ambifon (Helvepharm, Switz.) ,Amino MS (Larkhall Laboratories, UK) ,Biocarnil (Abiogen, Ital.) ,Calcioretard (Farmapros, Spain) ,Cerebrix (Roussel, Ital.) ,Champs C with Lysine (Upha, Indon.) ,Champs C with Lysine (Upha, Singapore) ,Coba-12 (Nordic, Canad.) ,Cold Sore Relief (Vitaplex, Austral.) ,Cold Sore Tablets (Vitaglow, Austral.) ,Combivit (Biomedica, Ital.) ,Corpotasin CL (Armstrong, Mex.) ,Curasten (Therabel, Fr.) ,Euzymina Lisina I (Menarini, Spain) ,Euzymina Lisina II (Menarini, Spain) ,Ferrochelate (David, India) ,Gliviton (SIFI, Ital.) ,Gliviton (SIFI, Ital.) ,Klorvess (Novartis, USA) ,Klorvess (Novartis, USA) ,Logical (Serum Institute, India) ,Lysine Hydrochloride Tablets USP 32,Malandil (Bohm, Spain) ,Oroticon Lisina (Also, Ital.) ,Pranzo (Vinas, Spain) ,Revitalose (UCB, Fr.) ,Tonoferon (East India Pharma, India) ,Vitonisan B (Septa, Spain)

Profile
Lysine is a basic amino acid that is an essential constituent of the diet. Lysine acetate and lysine hydrochloride are used as dietary supplements.

Lysinuric protein intolerance.
For mention of the use of lysine to correct lysine deficiency in lysinuric protein intolerance, see Hyperammonaemia, under Citrulline, Citrulline.

Proline

Physical And Pharmaceutical Properties
Name Status:USAN, rINN
Synonyms: P;Pro;Proliini;Prolin;Prolina;Prolinas;L-Proline;Prolinum
Chemical Name: L-Pyrrolidine-2-carboxylic acid
Molecular Formula: C5H9NO2
Molecular Weight:115.1
CAS Registry: 147-85-3
Pharmacopoeias:In Chin., Eur. (see About Martindale), and US.
Ph. Eur. 6.4 (Proline). A white or almost white, crystalline powder or colourless crystals. Very soluble in water; freely soluble in alcohol. Protect from light.
USP 32 (Proline). White, odourless crystals. Freely soluble in water and in dehydrated alcohol; insoluble in butyl alcohol, in ether, and in isopropyl alcohol.

Proprietary Names
Creme Laser Hidrante (Dermoteca, Port.)

Profile
Proline is a cyclic non-essential amino acid. It is used as a dietary supplement.

Threonine

Physical And Pharmaceutical Properties
Name Status:USAN, rINN
Synonyms: β-Methylserine;T;Thr;Threonin;Thréonine;L-Threonine;Threoninum;Treoniini;Treonin;Treonina;Treoninas
Chemical Name: L-2-Amino-3-hydroxybutyric acid
Molecular Formula: C4H9NO3
Molecular Weight:119.1
CAS Registry: 72-19-5
Pharmacopoeias:In Chin., Eur. (see About Martindale), Jpn, and US.
Ph. Eur. 6.4 (Threonine). A white or almost white, crystalline powder or colourless crystals. Soluble in water; practically insoluble in alcohol. A 2.5% solution in water has a pH of 5.0 to 6.5. Protect from light.
USP 32 (Threonine). White, odourless crystals. Freely soluble in water; insoluble in dehydrated alcohol, in chloroform, and in ether. pH of a 5% solution in water is between 5.0 and 6.5.

Proprietary Names
Stimolfit (Body Spring, Ital.) ,Vitonisan B (Septa, Spain)

Profile
Threonine is an amino acid that is an essential constituent of the diet. It is used as a dietary supplement.
Threonine has been investigated for the treatment of various spastic disorders.