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].

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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 small intestine lumen to intestinal cells via active transport. Metabolism/Metabolites Liver

The intraperitoneal LD50 in rats was 5223 mg/kg; behavioral changes included altered sleep duration (including changes in the righting reflex); lung, thoracic, or respiratory symptoms included 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 regulation, normalizes neuronal overexcitation, and does not cause sedation. Its stereoselectivity (D-isomer) gives it metabolic stability relative to L-methionine [1]. Mechanistically, it resists cisplatin toxicity through the following pathways: 1) competitive binding with plasma proteins; 2) scavenging cisplatin-induced reactive oxygen species; 3) maintaining intracellular glutathione reserves [2]. In preclinical models, D-methionine has shown clinical application potential as a chemoprotective adjuvant, protecting cognitive function during platinum-based chemotherapy without affecting antitumor efficacy [3]. D-methionine is the optically active form of methionine with the D conformation. It is a methionine and also a D-α-amino acid. It is the conjugate base of D-methionine ononium. It is the conjugate acid of D-methionine, an enantiomer of L-methionine, and also a zwitterion of D-methionine.
It is a sulfur-containing essential amino acid, crucial for many bodily functions. It is a heavy metal chelator.
D-methionine is a metabolite of Escherichia coli (K12 strain, MG1655 strain), present in or produced by E. coli.
D-methionine has also been reported in Pinus tabuliformis, Cyperus rotundus, and some other organisms with relevant data.
Methionine is one of the nine essential amino acids for humans (primarily obtained through food) and is essential for growth and tissue repair. As a sulfur-containing amino acid, methionine can improve the elasticity and suppleness of skin and hair, and strengthen nails. The sulfur provided by methionine participates in various detoxification processes, protects cells from pollutants, slows cell aging, and is crucial for the absorption and bioavailability of selenium and zinc. Methionine can chelate heavy metals such as lead and mercury, promoting their excretion. It also has a lipotropic effect, preventing excessive fat accumulation in the liver. (NCI04)
D-methionine preparation MRX-1024 is a proprietary oral D-methionine preparation with antioxidant and anti-mucositis activities. D-methionine preparation MRX-1024 selectively protects the oral mucosa from the toxic effects of chemotherapy and radiotherapy without affecting its antitumor activity. D-methionine can be converted to its L-isomer in vivo, especially in the presence of L-methionine deficiency; both isomers possess antioxidant activity, possibly attributable in part to their sulfur groups and chelating properties. L-methionine is an essential amino acid that helps maintain the ratio of reduced to oxidized glutathione in cells under oxidative stress and provides L-cysteine for glutathione synthesis. L-methionine is a sulfur-containing essential L-amino acid crucial for many bodily functions. Pharmaceutical Indications Used for protein synthesis, including the formation of S-adenosylmethionine (SAMe), L-homocysteine, L-cysteine, taurine, and sulfate. Mechanism of Action The possible anti-hepatotoxic mechanism of L-methionine is not fully understood. It is believed that the liver's metabolism of high doses of acetaminophen leads to decreased hepatic glutathione levels and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may possess antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. The antioxidant activity of L-methionine and its metabolites appears to be the reason for its potential anti-hepatotoxic effects. Recent studies have shown that methionine itself possesses free radical scavenging activity due to its sulfur-containing compounds and 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).

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