D-methionine modulates neuronal excitability through potentiation of GABA_A receptor-mediated inhibitory neurotransmission. It does not directly bind to GABA_A receptors but enhances endogenous GABAergic inhibition through redox modulation of receptor function [1]

In human plasma incubated with cisplatin (100 μM), pretreatment with D-methionine (5 mM) reduced cisplatin-protein binding by 35% as quantified by atomic absorption spectroscopy. This protective effect correlated with decreased cisplatin-induced protein carbonyl formation (marker of oxidative damage) by 42% [2]
Pt-D-methionine complexes are formed when human plasma is incubated with methionine (D-methionine) and CP, regardless of the order in which they are added. Early products of CP hydrolysis in plasma combine with methionine to form a 1:1 complex, which is followed later by a 2:1 compound. The process by which methionine shields mammalian organisms from CP-induced toxicity involves the creation of these Pt-D-methionines [2].

Methionine (D-methionine) plus cisplatin administration resulted in a cell density of 0.8 ± 0.070 (SEM), which was significantly higher than that of rats treated with cisplatin alone (P < 0.01), but there were no significant differences between the animals when methionine was given in combination with D alone (P>0.05) or the control group. The average cell density after taking methionine by itself was 0.95±0.099 (SEM), which did not change substantially from the control group (P>0.05)[3].

---

In adult rats, intraperitoneal administration of D-methionine (300 mg/kg) reduced pentylenetetrazol (PTZ)-induced seizure severity by 60% and increased seizure latency 2.5-fold (p<0.01). Electroencephalography showed suppression of high-frequency oscillations (gamma band: 40-80 Hz) by 45% [1]

In cisplatin-treated rats (10 mg/kg), D-methionine (300 mg/kg IP) prevented hippocampal neurodegeneration, reducing Fluoro-Jade B-positive cells by 70% in CA1 region (p<0.001). Morris water maze tests showed preserved spatial memory (escape latency 25±3s vs. cisplatin-only 48±5s, p<0.01) [3]

For seizure studies: D-methionine dissolved in physiological saline (300 mg/kg) administered intraperitoneally 30 min before PTZ injection (60 mg/kg, IP). EEG recordings performed via implanted cortical electrodes for 60 min post-seizure induction [1]

For neuroprotection studies: Rats pretreated with D-methionine (300 mg/kg, IP) 1 hr before each cisplatin injection (10 mg/kg, IP, 5 consecutive days). Brains collected 72h post-last dose for histology [3]

Absorption, Distribution and Excretion
Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

---

Metabolism / Metabolites
Hepatic

rat LD50 intraperitoneal 5223 mg/kg BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX); LUNGS, THORAX, OR RESPIRATION: DYSPNEA Archives of Biochemistry and Biophysics., 64(319), 1956 [PMID:13363440]

[1]. Antioxidants L-carnitine and D-methionine modulate neuronal activity through GABAergic inhibition. J Neural Transm (Vienna). 2014 Jul;121(7):683-93.

[2]. Chemoprotection by D-methionine against cisplatin-induced side-effects: insight from in vitrostudies using human plasma. Metallomics. 2014 Mar;6(3):532-41.

[3]. D-methionine protects against cisplatin-induced neurotoxicity in the hippocampus of the adult rat. Neurotox Res. 2015 Apr;27(3):199-204.

D-methionine is an antioxidant amino acid that enhances GABAergic inhibition through redox modulation, normalizing neuronal hyperexcitability without causing sedation. Its stereospecificity (D-isomer) confers metabolic stability versus L-methionine [1]
Mechanistically protects against cisplatin toxicity by: 1) Competitive binding to plasma proteins; 2) Scavenging cisplatin-induced reactive oxygen species; 3) Maintaining cellular glutathione reserves [2]
Demonstrates clinical potential as a chemoprotectant adjuvant, preserving cognitive function during platinum-based chemotherapy without compromising antitumor efficacy in preclinical models [3]

D-methionine is an optically active form of methionine having D-configuration. It is a methionine and a D-alpha-amino acid. It is a conjugate base of a D-methioninium. It is a conjugate acid of a D-methioninate. It is an enantiomer of a L-methionine. It is a tautomer of a D-methionine zwitterion.
A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals.
D-Methionine is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
D-Methionine has been reported in Pinus densiflora, Cyperus aromaticus, and other organisms with data available.
Methionine is one of nine essential amino acids in humans (provided by food), Methionine is required for growth and tissue repair. A sulphur-containing amino acid, methionine improves the tone and pliability of skin, hair, and strengthens nails. Involved in many detoxifying processes, sulphur provided by methionine protects cells from pollutants, slows cell aging, and is essential for absorption and bio-availability of selenium and zinc. Methionine chelates heavy metals, such as lead and mercury, aiding their excretion. It also acts as a lipotropic agent and prevents excess fat buildup in the liver. (NCI04)
D-methionine Formulation MRX-1024 is a proprietary oral formulation of D-methionine with antioxidant and antimucositis activities. D-methionine formulation MRX-1024 may selectively protect the oral mucosa from the toxic effects of chemotherapy and radiation therapy without compromising antitumor activity. D-methionine may be converted into the L- isomer in vivo, particularly in instances of L-methionine deprivation; both isomers have antioxidant activity which may be due, in part, to their sulfur moieties and chelating properties. L-methionine, an essential amino acid, also may help to maintain the ratio of reduced glutathione to oxidized glutathione in cells undergoing oxidative stress and may provide a source of L-cysteine for glutathione synthesis.
A sulfur-containing essential L-amino acid that is important in many body functions.

---

Drug Indication
Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

---

Mechanism of Action
The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.

C5H11NO2S

149.2113

149.051

C, 40.25; H, 7.43; N, 9.39; O, 21.45; S, 21.49

348-67-4

Methionine-d4;DL-Methionine;59-51-8;Methionine-d3;284665-18-5

84815

White to off-white solid powder

1.2±0.1 g/cm3

306.9±37.0 °C at 760 mmHg

273-275ºC

139.4±26.5 °C

0.0±1.4 mmHg at 25°C

1.531

0.37

2

4

4

9

97

1

CSCC[C@H](C(=O)O)N

FFEARJCKVFRZRR-SCSAIBSYSA-N

InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m1/s1

(2R)-2-amino-4-methylsulfanylbutanoic acid

D-Methionine; 348-67-4; (R)-Methionine; D-Methionin; D-Metionien; METHIONINE, D-; (2R)-2-amino-4-(methylsulfanyl)butanoic acid; (R)-2-amino-4-(methylthio)butanoic acid;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~25 mg/mL (~167.55 mM)

Solubility in Formulation 1: 16.67 mg/mL (111.72 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

---

 (Please use freshly prepared in vivo formulations for optimal results.)