Copper (Cu²⁺); metal toxicity targets. DL-Penicillamine is a copper chelating agent that binds to copper ions. By chelating copper, the compound can reduce copper toxicity and facilitate its excretion. It has antidotal effects in thallotoxicosis when co-treated with Prussian blue. The compound can cause pyridoxine deficiency, induce optic axial neuritis, and depress the primary immune response.

DL-Penicillamine is a copper chelating agent. It has antidotal effects in thallotoxicosis rats when co-treated with Prussian blue. The compound can cause pyridoxine deficiency and induce optic axial neuritis. It can also depress the primary immune response. Its in vitro activity includes copper chelation and potential effects on immune cells.

DL-Penicillamine (25 mg/kg; ip; twice daily, for 5 days) has antidotal benefits when combined with Prussian blue in rats with thallotoxicosis[2].

---

In vivo, DL-penicillamine has antidotal effects in thallotoxicosis rats when co-treated with Prussian blue. It can cause pyridoxine deficiency and induce optic axial neuritis. It can also depress the primary immune response. The compound is not used therapeutically in its racemic form but serves as a research tool for studying copper chelation and metal toxicity.

Non-cell-based assays for DL-penicillamine include copper chelation assays using colorimetric or fluorescent indicators. The compound’s ability to bind copper is measured by changes in absorbance or fluorescence. Thallium toxicity models can be used to assess antidotal effects. Standard analytical methods including HPLC, NMR, and mass spectrometry are used for compound characterization and purity assessment.

Cell-based assays for DL-penicillamine use various cell lines to assess copper chelation and its effects on cellular copper homeostasis. Cells are treated with the compound, and intracellular copper levels are measured using atomic absorption spectroscopy or fluorescent probes. Immune cell function assays can be used to assess effects on the primary immune response. Cytotoxicity is assessed using standard cell viability assays.

Animal/Disease Models: Male Wistar rats, NIH strain (intoxicated by ip injection of 32 mg/kg thallium (I) acetate)[2]
Doses: 25 mg/kg
Route of Administration: ip; twice (two times) daily, for 5 days
Experimental Results: diminished slightly the thallium content in blood, organs and brain. Increased the probability survival when co- treated with Prussian blue (50 mg/kg; po).

---

In vivo studies of DL-penicillamine are conducted in animal models of thallotoxicosis to assess its antidotal effects when co-treated with Prussian blue. The compound’s effects on pyridoxine levels, optic nerve function, and immune response can be assessed in animal models. Standard protocols for these models involve administration of the compound followed by measurement of relevant endpoints.

DL-Penicillamine has a molecular formula of C₅H₁₁NO₂S and a molecular weight of 149.21 g/mol. Purity is ≥97%. It is the racemic mixture of D-penicillamine and L-penicillamine. The compound should be stored as a powder at -20°C. It is intended for research use only.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that penicillamine is undetectable in breast milk, and no adverse reactions have been reported in infants breastfed by mothers taking the drug. Copper and zinc levels in the breast milk of some mothers taking penicillamine were reduced. Penicillamine has a good safety profile when used with multiple infants during lactation. Based on the available data, the use of penicillamine during lactation appears to be acceptable.
◉ Effects on Breastfed Infants
A woman with cystinuria took 1500 mg of penicillamine daily and breastfed for 3 months; the infant did not experience any significant adverse reactions.
A woman with Wilson's disease took an unspecified dose of penicillamine and breastfed her infant. The infant's serum copper and zinc levels were normal. The infant was well-fed and developing normally.
Another woman breastfed two infants while receiving 750 mg of penicillamine daily for Wilson's disease after two pregnancies. One infant developed persistent jaundice, but this was unlikely to be related to penicillamine. A Turkish center reported 23 infants born to mothers with Wilson's disease over a 20-year period. 21 of these infants received daily treatment with 600 mg penicillamine and 100 mg zinc. All infants were breastfed (the extent and duration of breastfeeding were not specified). One premature infant died three weeks after birth (the mother's medication was not specified), but another infant remained symptom-free during a follow-up period of an average of 51 months (range 13 to 105 months). A German center reported 32 patients with Wilson's disease who were pregnant. 13 patients received daily doses of penicillamine ranging from 600 to 1200 mg. Of the 31 women who delivered live infants, 27 breastfed (the extent of breastfeeding was not specified). Four infants developed neonatal jaundice, but its relationship to penicillamine could not be determined. The exact number of women who breastfed while taking penicillamine was not specified in the report. Seven women with Wilson's disease received 300 to 800 mg of penicillamine daily. Maternal reports indicated that all infants developed normally. ◉ Effects on Lactation and Breast Milk
Some case reports and studies have shown that copper and zinc concentrations in breast milk decrease during penicillamine treatment for Wilson's disease.
A more recent study compared copper concentrations in the breast milk of seven mothers receiving penicillamine with 25 control mothers without Wilson's disease. The colostrum (days 0-4 postpartum) from women receiving penicillamine showed slightly higher than normal copper concentrations. Despite lower maternal serum copper concentrations, copper and zinc concentrations in mature milk (days 14 and beyond postpartum) were normal in all mothers receiving penicillamine.

---

DL-Penicillamine is a copper chelating agent that can cause pyridoxine deficiency, optic axial neuritis, and depression of the primary immune response. It has antidotal effects in thallotoxicosis. The compound is intended for research use only and is not for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound.

[1]. TU J, BLACKWELL RQ, LEE PF. DL-penicillamine as a cause of optic axial neuritis. JAMA. 1963 Jul 13;185:83-6.

[2]. Additive effect of DL-penicillamine plus Prussian blue for the antidotal treatment of thallotoxicosis in rats. Environ Toxicol Pharmacol. 2011 Nov;32(3):349-55.

[3]. Huebner Kf, Gengozian N. Depression Of The Primary Immune Response By Dl-Penicillamine. Proc Soc Exp Biol Med. 1965 Feb;118:561-5.

Penicillamine is an α-amino acid with a β-position substituted with a thiol group. It is a non-protein α-amino acid and thiol. 3-Mercapto-D-valine is the most characteristic degradation product of penicillin antibiotics. It is used as an antirheumatic drug and a chelating agent for Wilson's disease. See also: penicillamine (note moved to); L-penicillamine (note moved to).

---

DL-Penicillamine ((±)-Penicillamine) is the racemic mixture of D-penicillamine and L-penicillamine. It is a copper chelating agent with antidotal effects in thallotoxicosis when co-treated with Prussian blue. The compound can cause pyridoxine deficiency and induce optic axial neuritis and can depress the primary immune response. It is used as a research tool for studying copper chelation and metal toxicity and is for research use only.

C5H11NO2S

149.21

149.051

52-66-4

Penicillamine;52-67-5;Penicillamine-d3

4727

Solid powder

1.2±0.1 g/cm3

251.8±35.0 °C at 760 mmHg

198.5 °C

106.1±25.9 °C

0.0±1.1 mmHg at 25°C

1.528

0.93

3

4

2

9

124

0

CC(C)(C(C(=O)O)N)S

VVNCNSJFMMFHPL-UHFFFAOYSA-N

InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)

2-amino-3-methyl-3-sulfanylbutanoic 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: 33.33 mg/mL (223.38 mM)

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 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).

View More

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 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).

View More

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.)