Physicochemical Properties
| Molecular Formula | C12H21N |
| Molecular Weight | 179.30184 |
| Exact Mass | 179.167 |
| CAS # | 13392-28-4 |
| Related CAS # | Rimantadine hydrochloride;1501-84-4;Rimantadine-d4 hydrochloride;350818-67-6 |
| PubChem CID | 5071 |
| Appearance | Colorless to light yellow liquid |
| Density | 1.033 |
| Boiling Point | 248ºC |
| Melting Point | 375°C(lit.) |
| Flash Point | 99ºC |
| Vapour Pressure | 0.0249mmHg at 25°C |
| Index of Refraction | 1.539 |
| LogP | 4.052 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 13 |
| Complexity | 180 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CC(C1(C[C@H](C2)C3)C[C@H]3C[C@H]2C1)N |
| InChi Key | UBCHPRBFMUDMNC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C12H21N/c1-8(13)12-5-9-2-10(6-12)4-11(3-9)7-12/h8-11H,2-7,13H2,1H3 |
| Chemical Name | 1-(1-adamantyl)ethanamine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Well absorbed, with the tablet and syrup formulations being equally absorbed after oral administration. Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug. Protein binding: Moderate (approximately 40%). Distribution: VolD - Adults: 17 to 25 L/kg. Children: MEan of 289 L. Concentrations in the nasal mucus average 50% higher than those in plasma. Well absorbed; tablets and syrup are absorbed equally well after oral administration. Time to peak concentration: 1 to 4 hours. For more Absorption, Distribution and Excretion (Complete) data for RIMANTADINE (11 total), please visit the HSDB record page. Metabolism / Metabolites Following oral administration, rimantadine is extensively metabolized in the liver with less than 25% of the dose excreted in the urine as unchanged drug. Glucuronidation and hydroxylation are the major metabolic pathways. Rimantadine hydrochloride is metabolized extensively in the liver to at least 3 hydroxylated metabolites. These have been designated as conjugated and unconjugated 3-, 4a-, and 4beta-hydroxylated metabolites. A glucuronide conjugate of rimantadine also has been identified. Extensively metabolized in the liver; glucuronidation and hydroxylation are the major metabolic pathways. Biological Half-Life 25 to 30 hours in young adults (22 to 44 years old). Approximately 32 hours in elderly (71 to 79 years old) and in patients with chronic liver disease. Approximately 13 to 38 hours in children (4 to 8 years old). Young adults (22 to 44 years old): 25 to 30 hours. Older adults (71 to 79 years old) and patients with chronic liver disease: Approximately 32 hours. Children (4 to 8 years old): 13 to 38 hours. |
| Toxicity/Toxicokinetics |
Hepatotoxicity Despite widespread use, there is little evidence that rimantadine when given orally causes liver injury, either in the form of serum enzyme elevations or clinically apparent liver disease. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on rimantadine during breastfeeding. The manufacturer states that the drug should not be used during breastfeeding. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Approximately 40% over typical plasma concentrations. Interactions Concurrent use of a single dose of rimantadine with cimetidine reduces rimantadine clearance by 18% in healthy adults; the clinical significance si thought to be minimal at this time. Because influenza antiviral agents reduce replication of influenza viruses, do not administer influenza virus vaccine live intranasal until at least 48 hours after rimantadine is discontinued and do not administer rimantadine until at least 2 weeks after administration of influenza virus vaccine live intranasal. Cimetidine Concurrent use of acetaminophen or aspirin with rimantadine reduces the peak serum concentration of rimantadine by approximately 11%; the clinical significance is thought to be minimal at this time. |
| References |
[1]. Tominack, R.L. and F.G. Hayden, Rimantadine hydrochloride and amantadine hydrochloride use in influenza A virus infections. Infect Dis Clin North Am, 1987. 1(2): p. 459-78. [2]. Children with influenza A infection: treatment with rimantadine. Pediatrics, 1987. 80(2): p. 275-82. |
| Additional Infomation |
1-(1-adamantyl)ethanamine is an alkylamine. An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. Rimantadine is an Influenza A M2 Protein Inhibitor. The mechanism of action of rimantadine is as a M2 Protein Inhibitor. Rimantadine is an antiviral agent used as therapy for influenza A. Rimantadine has not been associated with clinically apparent liver injury. Rimantadine is a cyclic amine and alpha-methyl derivative of amantadine with antiviral activity. Although the exact mechanism of action of rimantadine is not understood, this agent appears to exert its antiviral effect against influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the uncoating of the virus and subsequent release of infectious viral nucleic acids into the cytoplasm of infected cells. An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. See also: Rimantadine Hydrochloride (has salt form). Drug Indication For the prophylaxis and treatment of illness caused by various strains of influenza A virus in adults. FDA Label Mechanism of Action The mechanism of action of rimantadine is not fully understood. Rimantadine appears to exert its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating of the virus. The protein coded by the M2 gene of influenza A may play an important role in rimantadine susceptibility. Rimantadine is thought to exert its inhibitory effect early in the viral replicative cycle, possibly by blocking or greatly reducing the uncoating of viral RNA within host cells. Genetic studies suggest that a single amino acid change on the transmembrane portion of the M2 protein can completely eliminate influenza A virus susceptibility to rimantadine. Rimantadine, like amantadine, inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein. The M2 protein of influenza A functions as an ion channel and is important in at least 2 aspects of virus replication, disassembly of the infecting virus particle and regulation of the ionic environment of the transport pathway. By interfering with the ion channel function of the M2 protein, rimantadine inhibits 2 stages in the replicative cycle of influenza A. Early in the virus reproductive cycle, rimantadine inhibits uncoating of the virus particle, presumably by inhibiting the acid-mediated dissociation of the virion nucleic acid and proteins, which prevents nuclear transport of viral genome material. Rimantadine also prevents viral maturation in some strains of influenza A (e.g., H7 strains) by promoting pH-induced conformational changes in influenza A hemagglutinin during its intracellular transport late in the replicative cycle. Adsorption of the virus to and penetration into cells do not appear to be affected by rimantadine. In addition, rimantadine does not interfere with the synthesis of viral components (e.g., RNA-directed RNA polymerase activity). Therapeutic Uses Rimantadine is indicated for the prophylaxis of respiratory tract infections caused by influenza A virus in adults and children, and the treatment of respiratory tract infections caused by influenza A virus in adults./Included in US product labeling/ Prevent infection with various strains of influenza A virues Drug Warnings Swine influenza (H1N1) viruses contain a unique combination of gene segments that have not been reported previously among swine or human influenza viruses in the US or elsewhere. The H1N1 viruses are resistant to amantadine and rimantadine but not to oseltamivir or zanamivir. Elderly patients, particularly those in chronic care facilities, are more likely than younger adults or children to experience adverse effects associated with rimantadine, primarily central nervous system (CNS) and gastrointestinal side effects. FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./ Adverse CNS effects (e.g., nervousness, anxiety, impaired concentration, lightheadedness) are less common with usual dosages of rimantadine than amantadine, probably in part because of differences in the pharmacokinetics of the drugs. In a 6-week study of daily 200-mg prophylactic doses of rimantadine hydrochloride or amantadine hydrochloride in healthy adults, about 6 or 13% of patients receiving the respective drug discontinued therapy because of adverse CNS effects versus about 4% of those receiving placebo. While neuropsychiatric (e.g., delirium, marked behavioral changes) or psychomotor dysfunction has occurred in patients receiving amantadine, these effects have not been reported in patients receiving rimantadine. For more Drug Warnings (Complete) data for RIMANTADINE (13 total), please visit the HSDB record page. Pharmacodynamics Rimantadine, a cyclic amine, is a synthetic antiviral drug and a derivate of adamantane, like a similar drug amantadine. Rimantadine is inhibitory to the in vitro replication of influenza A virus isolates from each of the three antigenic subtypes (H1N1, H2H2 and H3N2) that have been isolated from man. Rimantadine has little or no activity against influenza B virus. Rimantadine does not appear to interfere with the immunogenicity of inactivated influenza A vaccine. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.5772 mL | 27.8862 mL | 55.7724 mL | |
| 5 mM | 1.1154 mL | 5.5772 mL | 11.1545 mL | |
| 10 mM | 0.5577 mL | 2.7886 mL | 5.5772 mL |