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At least 19 recordsLinked to original sources
PubMed1989

Determination of penicillamine, penicillamine disulfide and penicillamine-glutathione mixed disulfide by high-performance liquid chromatography with electrochemical detection.

Methodology is described for the simultaneous determination of D-penicillamine, penicillamine disulfide and the penicillamine-glutathione mixed disulfide, as well as glutathione and glutathione disulfide, in human plasma, erythrocytes and urine. The various thiols and disulfides are separated by reversed-phase ion-pairing liquid chromatography with detection by an electrochemical detector with dual gold/mercury amalgam electrodes in series. The thiols are detected at the downstream electrode; the disulfides are reduced at the upstream electrode and then detected as the thiols at the downstream electrode. Detection limits (at a signal-to-noise ratio of 2.0) are in the picomole range for 20 microliters of injected solution for all compounds except penicillamine disulfide, which has a detection limit of 600 pmol in 20 microliters. A convenient method is described for preparation of the penicillamine-glutathione mixed disulfide by thiol/disulfide exchange with standardization of the solution by 1H NMR spectroscopy.

Chromatography, High Pressure Liquid↗
PubMed1986

[The detection of antibodies against D-penicillamine. 3. Detection of antibodies against D-penicillamine in the serum of patients with Wilson's disease treated with D-penicillamine--preliminary results].

121 serum samples from 54 patients with Wilson's disease were tested for antibodies against D-penicillamine by indirect immunofluorescence (DASS-system). IgG antibodies were found in 44 serum samples from 16 patients (31% of all patients). The incidence of serum antibodies was higher in patients with side effects during therapy with D-penicillamine (10 of 13 patients 77%) compared to 6 of 39 15% in patients without side effects. The titre of antibodies was higher in patients with side effects. The antibodies bound complement demonstrated by double immunofluorescence. These observations indicate that complement binding IgG antibodies to D-penicillamine are involved in pathogenesis of side effects during therapy with D-penicillamine.

Antibodies↗
PubMed1984

[The detection of antibodies against D-penicillamine. 1. Coupling of D-penicillamine to various carriers and generation of antibodies against D-penicillamine conjugate].

D-Penicillamin as 2-substituted 5,5-Dimethyl-thiazolidine-4-carbonic acid has been bound to poly-L-lysin, human serum albumin and bovine gamma globulin by means of a water-soluble carbodiimid. The anti-bodies generated at animal tests by immunization of guinea pigs had been proved by means of the radial immune diffusion acc. to Ouchterlony [10].

Animals↗
PubMed2000

Penicillamine for rheumatoid arthritis.

OBJECTIVES: To estimate the short-term effects of D-penicillamine for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group's trials register, the Cochrane Controlled Trials Register, Medline up to and including December 1998 and Embase from 1988-1998. We also carried out a handsearch of the reference lists of the trials retrieved from the electronic search. SELECTION CRITERIA: All randomized controlled trials and controlled clinical trials comparing D-penicillamine against placebo in patients with rheumatoid arthritis. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two reviewers (CS, EB) and checked by a third (MS) using a validated quality assessment tool. Rheumatoid arthritis outcome measures were extracted from the publications for the six-month endpoint and stratified according to D-penicillamine dosages: low (<500mg/day), moderate (500 to <1000mg/day) and high (1000 mg/day or greater). Data was abstracted by one reviewer and checked by a second (CS, MS). The pooled analysis was performed using the standardized mean difference for joint counts, pain and global assessments. The weighted mean difference was used for erythrocyte sedimentation rate (ESR). Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. Fixed effects models were used throughout, since no statistical heterogeneity was found. MAIN RESULTS: Six trials were identified, with 425 patients randomized to D-penacillamine and 258 to placebo. A statistically significant benefit was observed for D-penicillamine when compared to placebo for all three-dose ranges and for most outcome measures including: tender joint counts, pain, physician's global assessments and ESR. The standardized weighted mean differences between treatment and placebo in moderate doses were -0. 51 [95% CI -0.88, -0.14] for tender joint counts, -0.56 (95% CI -0. 87, -0.26) for pain and -0.97 (95% CI -1.25, -0.70) for global assessment. The difference for ESR was -10.6 mm/hr. Similar results were observed for the higher dose group. Total withdrawals were significantly higher in the moderate and high dosage D-penicillamine groups (OR=1.63 and 2.13 respectively), mostly due to increased adverse reactions (OR = 2.60 and 4.95 respectively), including renal and hematological abnormalities. REVIEWER'S CONCLUSIONS: D-penicillamine appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. Its efficacy appears to be similar to that of other disease modifying anti-rheumatic drugs (DMARDs), but with a significantly higher toxicity. Its effects on long-term functional status and radiological progression are not clear from this review.

Antirheumatic Agents↗
PubMed1978

The effect of D-penicillamine on mitogen-induced human lymphocyte proliferation: synergistic inhibition by D-penicillamine and copper salts.

The effect of D-penicillamine on in vitro mitogen-triggered human peripheral blood lymphocyte DNA synthesis was examined. D-penicillamine caused a modest degree of inhibition of responsiveness. Since D-penicillamine avidly chelates copper, a possible additive effect of D-penicillamine and copper salts on mitogen-induced lymphocyte proliferation was investigated. The addition of various copper salts to D-penicillamine-containing cultures resulted in a marked augmentation in the degree of inhibition observed. Specificity for the synergy between D-penicillamine and copper was suggested by the failure of iron, zinc, or gold salts to augment the inhibition produced by D-penicillamine alone. However, a number of other thiols, but not disulfides, could substitute for D-penicillamine in inhibiting mitogen responsiveness in the presence of copper salts. Preincubation of peripheral blood mononuclear cells with D-penicillamine and CuSO4 resulted in diminished mitogen responsiveness on subsequent culture in the absence of the inhibitors. Data are presented to indicate that preincubation with D-penicillamine and CuSO4 directly affected the ability of the T lymphocytes to respond to mitogens but did not alter the capacity of the monocytes to act as accessory cells in this response.

Acetates↗
PubMed2000

D-Penicillamine for preventing retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death? SEARCH STRATEGY: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Two randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related. REVIEWER'S CONCLUSIONS: D-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

Chelating Agents↗
PubMed1980

Synthesis, pharmacological, conformational, and dynamic studies of the potent hormone antagonists [1-penicillamine, 4-threonine]-oxytocin and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin. Conformational and dynamic considerations in the design of antagonists.

The solid phase synthesis of [1-penicillamine, 4-threonine]-oxytocin and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin is reported. The two compounds have no in vitro milk ejecting activity and no in vivo or in vitro oxytocic activity, but both are potent antagonists in these three assay systems. In the in vitro oxytocic assay, [1-penicillamine, 4-threonine]- and [1-penicillamine, 2-phenylalanine, 4-threonine]-oxytocin have pA2 values of 7.55 +/- 0.04 and 7.67 +/- 0.02, respectively, and both inhibit the uterine contractile response to oxytocin in nonpregnant and pregnant rats. [1-Penicillamine, 2-phenylalanine, 4-threonine]-oxytocin has a weak antipressor activity and at high doses, consistently caused a weak and transient fall in blood pressure in the rat. Carbon-13 nuclear magnetic resonance chemical shift parameters and spin-lattice relaxation times (T1) indicate that these two new oxytocin antagonists have very similar conformation and dynamic properties to oxytocin inhibitors which have previously been examined. These results are discussed in terms of conformational and dynamic models of oxytocin antagonism at the uterus. It is suggested that conformational restrictions at the 2- and 4-positions of penicillamine-1 analogues of oxytocin are important to antagonist activity and potency.

Amino Acid Sequence↗
PubMed1975

The repair, protection and sensitization of papain with respect to inactivation by H2O2 and OH: effects of dithiothreitol, penicillamine, cystine and penicillamine disulphide.

While dithiothreitol repairs the peroxide-produced sulphenic acid derivative of papain in a fast reaction involving only one dithiothreitol molecule, penicillamine reacts with it to form papainCys25SSPen. Disulphide is also formed in the absence of peroxide (see article) by reactions of papainCys25S- AND PenS- radicals derived from -OH reactions in penicillamine-papain mixtures. A similar formation of papainCys25SSCys occurs in mixtures of cysteine and papain. However, unlike papainCys25SSCys, papainCys25SSPen cannot easily be restored to the active form of papain by the exchange reaction with CysSH, and this may have significance for an understanding of the sensitizing action of penicillamine observed in some in vivo systems. Under the action of OH radicals dithiothreitol has less of a tendency to form mixed disulphides and is more effective in repairing papain-OH intermediates than either cysteine or penicillamine. Due to secondary reactions of RSOH and other oxidized species the disulphides of cysteine and penicillamine are less effective than the sulphydryls in protecting papain against inactivation by -OH.

Cystine↗
PubMed1989

The effect of continuing penicillamine and gold treatment on the course of penicillamine and gold nephropathy.

The effect of continuing penicillamine or gold treatment was examined in 53 patients with biopsy proven penicillamine (32) or gold (21) nephropathy. Thirty-two patients stopped penicillamine or gold treatment as soon as proteinuria was detected whilst 21 patients continued treatment for periods of 2-11 months. The 24-hour creatinine clearance and urinary protein excretion were measured serially for a median period of 6 years. No significant differences were observed in the initial or maximum proteinuria, the duration of the proteinuria or in the initial or latest creatinine clearances between the groups of patients. These results indicate that penicillamine or gold treatment may be continued for short periods under close supervision despite moderate proteinuria without causing permanent renal damage. As several alternative non-nephrotoxic agents are available for the treatment of rheumatoid arthritis, continued treatment with penicillamine or gold despite proteinuria is seldom indicated.

Aged↗
PubMed1982

Penicillamine-induced myasthenia gravis: effects of penicillamine on acetylcholine receptor.

Autoimmune diseases, including myasthenia gravis, occur in patients treated with D-penicillamine. Because D-penicillamine might induce autoantibodies by the mechanism of antigenic alteration, we studied the reaction of D-penicillamine with purified acetylcholine receptor from Torpedo californica. We found that brief exposure to D-penicillamine resulted in its covalent attachment to two receptor subunits, alpha (40,000 daltons) and gamma (59,000 daltons), presumably by reduction and formation of mixed disulfides. Furthermore, D-penicillamine treatment resulted in a dramatic modification of the equilibrium acetylcholine binding properties of both purified receptor and receptor-rich membrane fragments.

Acetylcholine↗
PubMed1984

Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation.

D-Penicillamine and captopril, two drugs that induce autoimmune manifestations in man, were administered orally for 5 to 10 months to various strains of rats. Three to eight weeks after D-penicillamine administration in a dosage of 20 to 50 mg per day, 73% of Brown Norway (BN) rats became ill. The disease was characterized by weight loss, dermatitis, and a high mortality presumably caused by disseminated intravascular coagulation. Microscopy revealed widespread granulomatous and necrotic lesions. The plasma of these animals contained antinuclear antibodies and immune complexes. In the kidney deposits of IgG were found in a linear pattern along the glomerular basement membrane. IgG eluted from diseased kidneys bound both "in vitro" and "in vivo" to kidney basement membranes. BN rats initially receiving 5 mg of D-penicillamine per day and subsequently 20 and 50 mg per day did not develop disease. No adverse effects were noted in Lewis (LEW) and Sprague-Dawley (SD) rats treated with 20 or 50 mg of D-penicillamine per day, nor in BN and LEW rats treated with 20 mg of captopril per day.

Animals↗
PubMed1986

A prospective five-year comparison of treatment which included penicillamine with that excluding penicillamine in early rheumatoid arthritis. The Multicentre Trial Group.

Seventy-three patients with early, active rheumatoid arthritis (RA) were randomly allocated either to a group that received penicillamine or to a control group from which penicillamine was barred, any other second-line drug being permitted. Most (87%) of the controls received chrysotherapy at some stage. Clinical, serological and radiographic progress was observed for at least 5 years. Outcome after 5 years for the 27 remaining in the penicillamine group was compared with that for the 23 surviving controls. Both groups had improved clinically but deteriorated radiographically, with much individual variation. A subset of patients, mostly seronegative, who were radiographically normal at the outset remained so, regardless of treatment. Penicillamine was as effective as the control group treatments in relieving synovitis and as ineffective in arresting radiographic deterioration.

Adolescent↗
PubMed1985

D-penicillamine induced suppression of B cell function: in vivo effect of D-penicillamine.

We assessed the immunoglobulin secretory capacity of circulating B lymphocytes in 9 patients with classical rheumatoid arthritis (RA) before and after treatment with D-penicillamine. Peripheral blood lymphocytes (PBL) from patients with RA spontaneously synthesized more IgG and IgA than normals. The secretory rate of rheumatoid PBL could not be induced by the polyclonal activator, pokeweed mitogen (PWM). The presence of D-penicillamine in cultures significantly suppressed PWM stimulated immunoglobulin synthesis of control PBL but did not inhibit synthesis of mitogen stimulated RA PBL. After D-penicillamine therapy for 3 months immunoglobulin synthesis by PBL from patients with RA was reduced with or without PWM. The T mu:T gamma ratio was also decreased after therapy. These results support the hypothesis that D-penicillamine selectively impairs helper T cells in vivo, preventing the T dependent expansion and activation of B cells characteristic of RA.

Adult↗
PubMed1984

[Detection of antibodies against D-penicillamine. 2. Experimental animal proof of production of antibodies against D-penicillamine using indirect immunofluorescence with a DASS system].

Antibodies against D-penicillamine conjugates produced in animals be proved by indirect immunofluorescence by means of the DASS system (defined antigen substrate spheres). The artificial substrate (Sephadex G-25) has not been bound to the D-penicillamine conjugates used for immunization, but only to D-penicillamine, which justifies the assumption that antibodies against D-penicillamine could be registered and proved by the immunofluorescence test mentioned.

Animals↗
PubMed1980

Quantitative determination of small amounts of L-penicillamine in D-penicillamine after desulfurization with Raney nickel.

Commercially available D-penicillamine is desulfurized with Raney nickel at room temperature in aqueous solution. L-Valine derived from contaminating L-penicillamine is determined colorimetrically by the amino acid oxidase/peroxidase reaction, using 2,2'-azino-di-[3-ethyl-benz-thiazoline-sulfonate(6)] (ABTS). The procedure assures the quantitation of L-penicillamine contaminating D-penicillamine down to the level of 0.1%.

Drug Contamination↗
PubMed1980

[Administration of D-penicillamine instead of penicillin with fatal results: allergy of the delayed type with protracted shock as fatal complication of treatment with D-penicillamine for rheumatoid arthritis in a child (author's transl)].

Following one-week treatment with D-penicillamine for rheumatoid arthritis a seven-year-old girl died with the clinical features of protracted circulatory shock. Several doctors had mis-diagnosed the skin changes and mistakenly prescribed penicillamine, given for the rheumatoid arthritis, instead of plenicillin at the latter's dosage. By the administration of penicillamine a hypersensitivity reaction of the delayed type had been induced which ended fatally due to severe shock.

Arthritis, Rheumatoid↗
PubMed1978

[Studies on D-penicillamine (1): Inhibitory effect of D-penicillamine on the heat-Cu++ induced denaturation of human gamma-globulin (author's transl)].

The inhibitory effect of D-penicillamine on the denaturation of human gamma-globulin induced by heat and Cu++ was compared with the action of other agents such as antirheumatic drugs, anti-inflammatory drugs, SH reagents, SH inhibitors and chelating reagents. The denaturation of human gamma globulin was induced by Cu++ at 10 micrometer ("Cu++ induced denaturation") and was further increased by heating at 63 degrees C for 3 hr in the presence of Cu++ ("total denaturation"). Thus the value obtained by subtracting "Cu++ induced denaturation" from "total one" was designated as "thermal denaturation". D-Penicillamine enhanced "thermal denaturation" at a low concentration but inhibited it with increasing the concentration as well as L-cysteine. SH reagents such as thiomalic acid, 6-mercaptopurine inhibited "total" and "thermal" denaturation. SH inhibitors and protein binding reagents such as N-ethylmaleimide, trinitrobenzenesulfonic acid inhibited the "total" and "thermal" denaturation of the protein. Chelating reagents such as ethylenediamine tetraacetic acid, 8-hydroxyquinoline inhibited "total", "Cu++ induced" and "thermal" denaturation of the protein. Au+ inhibited "total denaturation", but not "Cu++ induced denaturation". On the other hand, Au+++ denaturated the protein considerably with or without heating, in the absence of Cu++ but dithiothreitol did so only with heating in the same condition. The anti-inflammatory drugs used herein had no effect on the protein denaturation. D-Penicillamine apparently prevents the denaturation of human gamma-globulin by the chelate formation with Cu++ and the binding to free protein SH, initiator for sulfhydryldisulfide interchange reaction.

Animals↗