Synonym
Methyldopate hydrochloride; Aldomet Ester hydrochloride; Aldomet; Methyldopa ethyl ester hydrochloride; Methyldopate HCl; EINECS 219-720-3;
IUPAC/Chemical Name
ethyl (S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoate hydrochloride
InChi Key
QSRVZCCJDKYRRF-YDALLXLXSA-N
InChi Code
InChI=1S/C12H17NO4.ClH/c1-3-17-11(16)12(2,13)7-8-4-5-9(14)10(15)6-8;/h4-6,14-15H,3,7,13H2,1-2H3;1H/t12-;/m0./s1
SMILES Code
N[C@](CC1=CC=C(O)C(O)=C1)(C)C(OCC)=O.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Methyldopate hydrochloride is an ethyl ester hydrochloride prodrug of α-Methyldopa (α-MD; HY-B0225).
In vitro activity:
After endothelial cellular networks appeared, trophoblast derived HTR-8/SVneo cells were co-cultured in the presence of clinically relevant doses of methyldopa, labetalol, hydralazine or clonidine for 24 hours. Methyldopa, labetalol, hydralazine and clonidine reversed the inhibitory effect of TNF-α on eNOS mRNA expression.
Reference: Clin Exp Pharmacol Physiol. 2017 Mar;44(3):421-427. https://pubmed.ncbi.nlm.nih.gov/27998008/
In vivo activity:
Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h.
Reference: Eur J Pharmacol. 1989 May 30;164(3):531-8. https://pubmed.ncbi.nlm.nih.gov/2767124/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
275.73
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Xu B, Bobek G, Makris A, Hennessy A. Antihypertensive methyldopa, labetalol, hydralazine, and clonidine reversed tumour necrosis factor-α inhibited endothelial nitric oxide synthase expression in endothelial-trophoblast cellular networks. Clin Exp Pharmacol Physiol. 2017 Mar;44(3):421-427. doi: 10.1111/1440-1681.12712. PMID: 27998008.
2. Kirtland HH 3rd, Mohler DN, Horwitz DA. Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia. N Engl J Med. 1980 Apr 10;302(15):825-32. doi: 10.1056/NEJM198004103021502. PMID: 6244489.
3. Kapoor V, Chalmers J. Correlation between fall in blood pressure and in vivo amine release after alpha-methylDOPA. Eur J Pharmacol. 1989 May 30;164(3):531-8. doi: 10.1016/0014-2999(89)90261-6. PMID: 2767124.
4. Fox GR, Virgo BB. The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat. Toxicol Appl Pharmacol. 1985 May;78(3):342-50. doi: 10.1016/0041-008x(85)90239-x. PMID: 4049384.
In vitro protocol:
1. Xu B, Bobek G, Makris A, Hennessy A. Antihypertensive methyldopa, labetalol, hydralazine, and clonidine reversed tumour necrosis factor-α inhibited endothelial nitric oxide synthase expression in endothelial-trophoblast cellular networks. Clin Exp Pharmacol Physiol. 2017 Mar;44(3):421-427. doi: 10.1111/1440-1681.12712. PMID: 27998008.
2. Kirtland HH 3rd, Mohler DN, Horwitz DA. Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia. N Engl J Med. 1980 Apr 10;302(15):825-32. doi: 10.1056/NEJM198004103021502. PMID: 6244489.
In vivo protocol:
1. Kapoor V, Chalmers J. Correlation between fall in blood pressure and in vivo amine release after alpha-methylDOPA. Eur J Pharmacol. 1989 May 30;164(3):531-8. doi: 10.1016/0014-2999(89)90261-6. PMID: 2767124.
2. Fox GR, Virgo BB. The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat. Toxicol Appl Pharmacol. 1985 May;78(3):342-50. doi: 10.1016/0041-008x(85)90239-x. PMID: 4049384.
1: Sousa e Silva JP, Lobo JS, Bonifácio MJ, Machado R, Falcão A, Soares-da-Silva P. In-vivo evaluation of prolonged release bilayer tablets of anti-Parkinson drugs in Göttingen minipigs. J Pharm Pharmacol. 2011 Jun;63(6):780-5. doi: 10.1111/j.2042-7158.2011.01278.x. Epub 2011 Apr 28. PubMed PMID: 21585375.
2: Khanmohammadi M, Mobedi E, Garmarudi AB, Mobedi H, Kargosha K. Simultaneous determination of levodopa and carbidopa in levodopa-carbidopa tablets by ATR-FTIR spectrometry. Pharm Dev Technol. 2007;12(6):573-80. PubMed PMID: 18161630.
3: Ali SA, Sami MA. Cyclic voltammetric study of alpha-methyldopa at carbon paste electrode. Pak J Pharm Sci. 2005 Jan;18(1):6-17. PubMed PMID: 16431377.
4: Ramadan A, El-Massik M, El-Khordagui L, Daabis N, Hammouda Y. Surface treatment: a potential approach for enhancement of solid-state photostability. Int J Pharm. 2006 Jan 13;307(2):141-9. Epub 2005 Nov 9. PubMed PMID: 16289573.
5: Okereke CS, Kirby L, Kumar D, Cullen EI, Pratt RD, Hahne WA. Concurrent administration of donepezil HCl and levodopa/carbidopa in patients with Parkinson's disease: assessment of pharmacokinetic changes and safety following multiple oral doses. Br J Clin Pharmacol. 2004 Nov;58 Suppl 1:41-9. PubMed PMID: 15496222; PubMed Central PMCID: PMC1884553.
6: Messiha FS. Neurotoxicological analyses of voluntary alcohol drinking by the rat. Neurobehav Toxicol Teratol. 1985 Mar-Apr;7(2):155-9. PubMed PMID: 3889685.
7: Ageel AM, Ginawi OT. Effects of methamphetamine and methyldopa on ethanol induced hypothermia in mice. Jpn J Pharmacol. 1985 Feb;37(2):137-42. PubMed PMID: 3999469.
8: Walash MI, Abou Ouf A, Salem FB. Spectrophotometric and titrimetric determination of certain adrenergic drugs, using organic brominating agents. J Assoc Off Anal Chem. 1982 Nov;65(6):1445-51. PubMed PMID: 6757241.
9: Reches A, Fahn S. 3-O-methyldopa blocks dopa metabolism in rat corpus striatum. Ann Neurol. 1982 Sep;12(3):267-71. PubMed PMID: 7137962.
10: McCrimmon DR, Lalley PM. Inhibition of respiratory neural discharges by clonidine and 5-hydroxytryptophan. J Pharmacol Exp Ther. 1982 Sep;222(3):771-7. PubMed PMID: 6286937.
11: Thiede HM, Kehr W. Endogenous dopa in rat brain. Occurrence, distribution and relationship to changes i catecholamine synthesis. Naunyn Schmiedebergs Arch Pharmacol. 1981 Jul;316(4):299-303. PubMed PMID: 6791035.
12: Pierach CA, Cardinal R, Bossenmaier I, Watson CJ. Comparison of the Hoesch and the Watson-Schwartz tests for urinary porphobilinogen. Clin Chem. 1977 Sep;23(9):1666-8. PubMed PMID: 890911.
