Acetylcarnitine
Identification
- Name
- Acetylcarnitine
- Accession Number
- DB08842
- Description
Acetylcarnitine is an investigational drug in the United states, Italy, United Kingdom, China, Israel, and Norway, and it is approved in Italy, Portugal, Argentina, Chile, Philippines, Australia, and India. Acetylcarnitine can be synthesized, but it is also naturally found in adequate amounts in healthy humans. In human plasma and tissues, acetylcarnitine is the most predominant acylated ester of carnitine, which is an amino acid derivative that is made in the kidney, liver, and brain from lysine and methionine. The main role of acetylcarnitine is to help transport fatty acids into the mitochondrial matrix where fatty acid metabolism occurs.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Acetylcarnitine (DB08842)
- Weight
- Average: 203.238
Monoisotopic: 203.115758031 - Chemical Formula
- C9H17NO4
- Synonyms
- acetyl-L-carnitine
- O-acetyl-L-carnitine
- O-Acetylcarnitine
Pharmacology
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Acetylcarnitine is not approved for any indication in the United states and Canada, but it is approved and indicated in Italy for cerebrovascular disorders, mental function disorders, peripheral nerve disorders, diabetic neuropathy, and nutritional supplementation; Portugal for mental function disorders; Argentina for cerebral vasculopathy, nutritional supplementation, and peripheral neuropathy; Chile for dementia; Philippines for cerebrovascular disorders and mental function disorders; Australia for nutritional supplementation; and India for nutritional supplementation to increase sperm count. Acetylcarnitine also has several potential therapeutic indications for which it is still being investigated: in Norway, acetylcarnitine is in a phase IV trial for prophylactic treatment of migraines; in Italy acetylcarnitine is in a phase II trial for use in patients with type 2 Diabetes Mellitus, a phase III trial for alleviating fatigue in patients with chronic hepatitis C, and for use in patients with Minimal Hepatic Encephalopathy; in the United States acetylcarnitine is in a phase II trial for the neurodegenerative disorder Progressive Supranuclear Palsy, a phase II and III trial for reducing peripheral neuropathy in cancer patients as an adjunct to chemotherapy, a phase I and II trial for treating patients in septic shock, a phase II trial for bipolar depression, a phase II trial to reduce oxidative stress in patients with Sickle Cell disease, a phase I and II trial for chronic fatigue syndrome, and a study for preventing nerve damage in HIV patients; in China acetylcarnitine is in a phase III trial for reducing peripheral neuropathy in cancer patients as an adjunct to chemotherapy; in the United Kingdom acetylcarnitine is being investigated for preventing nerve damage in HIV patients; and in Israel acetylcarnitine is being studied for the treatment of male infertility.
- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
The complete physiological effects of acetycarnitine are still being studied. What has been discovered so far is that acetylcarinitine has positive effects on mental fatigue, neurodegenerative disorders, cognitive functions, peripheral neuropathy, and sperm motility. Specifically, in one study involving patients with HIV, patients on acetylcarnitine supplementation had increased CD4 cells, decreased lymphocyte apoptosis, improved polyneuropathy and cardiovascular damage, and decreased triglyceride and TNF alpha levels in the blood. Another study showed that acetylcarnitine increased glucose disposal in type 2 diabetic patients through possibly increasing the activity of glycogen synthase.
- Mechanism of action
The mechanisms of action of acetylcarnitine have not been fully elucidated, but it seems that the main role of acetylcarnitine is to donate an acetyl group during fatty acid metabolism to help transport fatty acids, such as acetyl CoA, into the mitochondrial matrix where fatty acid metabolism occurs. Additionally several studies have found that separate from its metabolic role, acetylcarnitine has neuromodulatory, neurotrophic, and neuroprotective effects that most likely are involved in its positive effects in neurological diseases. In its role in treating male infertility, acetylcarnitine increases the active movement of sperm cells. One study has also mentioned a role for acetylcarnitine as an antioxidant. The study found that through the receptor, tyrosine kinase A, acetylcarnitine was able to decrease the production of free radicals, peroxidation of lipids, and oxidation of proteins as well as decrease glutathione levels and increase thioredoxin.
- Absorption
Acetylcarnitine supplements are absorbed in a similar manner to L-carnitine.
- Volume of distribution
- Not Available
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
Acetylcarnitine is eliminated in a similar manner as L-carnitine. Both of which are eliminated by the kidneys and involve tubular secretion.
- Half-life
- Not Available
- Clearance
- Not Available
- Adverse Effects
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- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- International/Other Brands
- Acilen (IFI (Italy)) / Actigeron (Bago (Chile)) / Branigen (Sigma-Tau (Italy)) / Branitil (OFF (Italy)) / Ceredor (IRBI (Italy)) / Fertilix (Fortbenton (Argentina)) / Lacetilina (Pentafarma (Portugal)) / Laremide (Lafedar (Argentina)) / Levocetile (Korea United (Philippines)) / Maxoza (Sun (India)) / Memorx IQ Plus (Gruppo Medica (Philippines)) / Memovigor (Euro-Pharma (Italy)) / Neurex (Beta (Argentina)) / Neuroactil (Bago (Argentina)) / Nicetile (Sigma-Tau (Italy)) / Normobren (Medosan (Italy)) / Phototrop (Tubilux (Italy)) / Zibren (Sigma-Tau (Italy))
Categories
- ATC Codes
- N06BX12 — Acetylcarnitine
- Drug Categories
- Amines
- Ammonium Compounds
- Central Nervous System Agents
- Diet, Food, and Nutrition
- Food
- Growth Substances
- Micronutrients
- Nervous System
- Nitrogen Compounds
- Nootropic Agents
- Onium Compounds
- Physiological Phenomena
- Psychoanaleptics
- Psychostimulants, Agents Used for Adhd and Nootropics
- Quaternary Ammonium Compounds
- Trimethyl Ammonium Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as acyl carnitines. These are organic compounds containing a fatty acid with the carboxylic acid attached to carnitine through an ester bond.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Fatty Acyls
- Sub Class
- Fatty acid esters
- Direct Parent
- Acyl carnitines
- Alternative Parents
- Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Carboxylic acid salts / Carboxylic acid esters / Carboxylic acids / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds show 1 more
- Substituents
- Acyl-carnitine / Aliphatic acyclic compound / Amine / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid ester / Carboxylic acid salt / Dicarboxylic acid or derivatives / Hydrocarbon derivative show 9 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- O-acetylcarnitine, O-acyl-L-carnitine (CHEBI:57589)
Chemical Identifiers
- UNII
- 6DH1W9VH8Q
- CAS number
- 3040-38-8
- InChI Key
- RDHQFKQIGNGIED-MRVPVSSYSA-N
- InChI
- InChI=1S/C9H17NO4/c1-7(11)14-8(5-9(12)13)6-10(2,3)4/h8H,5-6H2,1-4H3/t8-/m1/s1
- IUPAC Name
- (3R)-3-(acetyloxy)-4-(trimethylazaniumyl)butanoate
- SMILES
- CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C
References
- Synthesis Reference
Gu, Heng-da; Shi, Shuang; Yang, Ying; Shi, Zhao-xin; Yu, Zhan-long. Synthesis of acetyl-L-carnitine by direct acylation method. Shenyang Huagong Xueyuan Xuebao (2006), 20(2), 154-155, 160.
- General References
- Vermeulen RC, Scholte HR: Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 Mar-Apr;66(2):276-82. [PubMed:15039515]
- Ilias I, Manoli I, Blackman MR, Gold PW, Alesci S: L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. Mitochondrion. 2004 Jul;4(2-3):163-8. [PubMed:16120381]
- Salvioli G, Neri M: L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994;20(4):169-76. [PubMed:7813389]
- Rebouche CJ: Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004 Nov;1033:30-41. [PubMed:15591001]
- Virmani A, Binienda Z: Role of carnitine esters in brain neuropathology. Mol Aspects Med. 2004 Oct-Dec;25(5-6):533-49. [PubMed:15363640]
- Giancaterini A, De Gaetano A, Mingrone G, Gniuli D, Liverani E, Capristo E, Greco AV: Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients. Metabolism. 2000 Jun;49(6):704-8. [PubMed:10877193]
- Barhwal K, Hota SK, Jain V, Prasad D, Singh SB, Ilavazhagan G: Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation. Neuroscience. 2009 Jun 30;161(2):501-14. doi: 10.1016/j.neuroscience.2009.02.086. Epub 2009 Mar 24. [PubMed:19318118]
- Wilson AD, Hart A, Brannstrom T, Wiberg M, Terenghi G: Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J Plast Reconstr Aesthet Surg. 2007;60(2):114-8. Epub 2006 Jul 24. [PubMed:17223507]
- Ruggenenti P, Cattaneo D, Loriga G, Ledda F, Motterlini N, Gherardi G, Orisio S, Remuzzi G: Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy. Hypertension. 2009 Sep;54(3):567-74. doi: 10.1161/HYPERTENSIONAHA.109.132522. Epub 2009 Jul 20. [PubMed:19620516]
- Brayfield, Alison (2014). Martindale : The Complete Drug Reference (38th ed.). Pharmaceutical Press. [ISBN:978-0857111395]
- O'Neil, Maryadele J. (2013). The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals (15th ed.). Royal Society of Chemistry, The. [ISBN:978-1849736701]
- External Links
- Human Metabolome Database
- HMDB0000201
- KEGG Compound
- C02571
- PubChem Compound
- 7045767
- PubChem Substance
- 175427117
- ChemSpider
- 5406074
- 193
- ChEBI
- 57589
- ChEMBL
- CHEMBL1697733
- RxList
- RxList Drug Page
- Wikipedia
- Acetylcarnitine
- MSDS
- Download (39.8 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Fatigue / Fatigue in Workers With Chronic C Hepatitis / Work Productivity and Activity Impairment in Workers With Chronic C Hepatitis 1 4 Completed Treatment Migraine 1 4 Recruiting Treatment Mild Cognitive Impairment (MCI) 1 4 Unknown Status Treatment Alzheimer's Disease (AD) 1 3 Completed Treatment Daily Activity / Fatigue / Quality of Life 1 3 Completed Treatment High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus 1 3 Completed Treatment Sensory Peripheral Neuropathy 1 3 Completed Treatment Work Ability / Work Performance / Work Stress 1 3 Terminated Treatment Non-Small Cell Lung Carcinoma (NSCLC) 1 2 Completed Treatment Depression, Bipolar 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule, for solution Oral 500 MG Tablet, delayed release 500 MG Granule 500 MG Injection, powder, for solution Intramuscular; Intravenous 500 MG/5ML Powder 500 MG/5ML Capsule Oral 100 mg Capsule Oral 400 mg Injection Intramuscular 500 mg Injection Intramuscular 500 mg/4ml Injection, powder, for solution Intramuscular; Intravenous 500 MG/4ML Powder, for solution Oral 308 MG/ML Powder, for solution Oral 500 MG Tablet Oral 250 MG Tablet, delayed release Oral 500 MG Capsule Oral 500 mg Tablet Oral 500 MG - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 145°C From The Merck Index. water solubility Very soluble in water and alcohol. From The Merck Index. - Predicted Properties
Property Value Source Water Solubility 0.355 mg/mL ALOGPS logP -2.4 ALOGPS logP -4.4 ChemAxon logS -2.9 ALOGPS pKa (Strongest Acidic) 4.09 ChemAxon pKa (Strongest Basic) -7 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 66.43 Å2 ChemAxon Rotatable Bond Count 6 ChemAxon Refractivity 72.64 m3·mol-1 ChemAxon Polarizability 20.89 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9965 Blood Brain Barrier + 0.8614 Caco-2 permeable + 0.5175 P-glycoprotein substrate Non-substrate 0.5593 P-glycoprotein inhibitor I Non-inhibitor 0.9272 P-glycoprotein inhibitor II Non-inhibitor 0.6465 Renal organic cation transporter Non-inhibitor 0.916 CYP450 2C9 substrate Non-substrate 0.8267 CYP450 2D6 substrate Non-substrate 0.8471 CYP450 3A4 substrate Substrate 0.5303 CYP450 1A2 substrate Non-inhibitor 0.9367 CYP450 2C9 inhibitor Non-inhibitor 0.9236 CYP450 2D6 inhibitor Non-inhibitor 0.9355 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8818 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9761 Ames test Non AMES toxic 0.8217 Carcinogenicity Carcinogens 0.5207 Biodegradation Ready biodegradable 0.8743 Rat acute toxicity 2.3717 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9728 hERG inhibition (predictor II) Non-inhibitor 0.9018
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Symporter activity
- Specific Function
- Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
- Gene Name
- SLC22A5
- Uniprot ID
- O76082
- Uniprot Name
- Solute carrier family 22 member 5
- Molecular Weight
- 62751.08 Da
References
- Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100]
- Kobayashi D, Tamai I, Sai Y, Yoshida K, Wakayama T, Kido Y, Nezu J, Iseki S, Tsuji A: Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa. Reproduction. 2007 Nov;134(5):651-8. [PubMed:17965255]
- Kind
- Protein
- Organism
- Mouse
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Cation:cation antiporter activity
- Specific Function
- Sodium-ion independent, medium affinity carnitine transporter. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of ...
- Gene Name
- Slc22a21
- Uniprot ID
- Q9WTN6
- Uniprot Name
- Solute carrier family 22 member 21
- Molecular Weight
- 63320.215 Da
References
- Kobayashi D, Tamai I, Sai Y, Yoshida K, Wakayama T, Kido Y, Nezu J, Iseki S, Tsuji A: Transport of carnitine and acetylcarnitine by carnitine/organic cation transporter (OCTN) 2 and OCTN3 into epididymal spermatozoa. Reproduction. 2007 Nov;134(5):651-8. [PubMed:17965255]
Drug created on February 27, 2013 21:42 / Updated on June 12, 2020 16:52