D-Penicillamine

The somewhat paradoxical situation of having enhanced copper levels in advanced arthritis, and the moderate advantages of using copper complexes in treatment, is mirrored by the apparent contradiction of D-penicillamine efficacy, despite its clinical use for treatment and excretion of excess copper in Wilson s disease [46]. There is little evidence that penicillamine copper complexes have any relevance in vivo. Ceruloplasmin copper is unavailable for chelation and, indeed, D-penicillamine is not particularly effective at scavenging Cu(II) from BSA [84]. 

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The amino acids L-leucine, T-phenylalanine, L-tyrosine, and L-tryptophan all taste bitter, whereas their D-enantiomers taste sweet (5) (see Amino ACIDS). D-Penicillamine [52-67-5] a chelating agent used to remove heavy metals from the body, is a relatively nontoxic dmg effective in the treatment of rheumatoid arthritis, but T.-penicillamine [1113-41 -3] produces optic atrophy and subsequent blindness (6). T.-Penicillamine is roughly eight times more mutagenic than its enantiomer. Such enantioselective mutagenicity is likely due to differences in renal metaboHsm (7). (R)-ThaHdomide (3) is a sedative—hypnotic (3)-thaHdomide (4) is a teratogen (8). 

The following trivial names have been assigned to the penicillin transformation products shown (6), benzylpenicilloate (7), benzylpenaldic acid (8), D-penicillamine (9), a-methyl D-a-benzylpenicilloate (10), benzylpenillic acid (11), benzylpenillamine (12), benzyl-isopenillic acid (13), benzylpenilloic acid (14), benzylpenilloaldehyde (15), benzylpenicil-lenic acid (16) benzylpenillonic acid methyl ester and (17), dethiobenzylpenicillin methyl ester. 

Penicilloic acid 5, the substrate for the projected lactamization reaction, could be derived from the suitably protected intermediate 6. Retrosynthetic disassembly of 6, in the manner illustrated, provides D-penicillamine hydrochloride (7) and tert-butyl phthalimido-malonaldehydate (8) as potential building blocks. In the synthetic direction, it is conceivable that the thiol and amino groupings in 7 could be induced to converge upon the electrophilic aldehyde carbonyl in 8 to give thiazolidine 6 after loss of a molecule of water. 

Systemic muscle damage, often associated with pain and discomfort, is a well known problem associated with specific drugs such as epsilon amino caproic acid (EACA), clofibrate, emetine, vincristine, chloroquine, D-penicillamine, and anabolic steroids. Notes on each of these drugs follow, but for a detailed discussion of drug-induced muscle damage refer to Argov and Mastaglia (1988) and Harris and Blain (1990). 

D-penicillamine a well-recognized complication of the use of D-penicillamine is a myasthenic syndrome. Most reported cases of myasthenic syndrome are women and the ocular muscles appear to be particularly commonly affected at early stages of the abnormality. The onset of the myasthenic syndrome can range between a few months and many years, and is not always reversible. There is a clear immunological basis to this problem, because it is associated with raised anti-acetylcholine receptor antibodies circulating in the serum. Antibody levels fall when the drug is withdrawn, and this, in turn, is associated with clinical improvement. How the... 

CHN 74-90-8) see L-Alanine Alfentanil Dimethadione Edetic acid Ibuprofen Indanorex Mecamylamine Molsidomine Nadoxolol D-Penicillamine Phensuximide L-Tryptophan Vetrabutine hydrogen peroxide... 

CiiHuOn 112-05-0) see Azelaic acid D-penicillamine Hg complex (CjH Cl2HgN02S 14062-65-8) see D-Penicillamine D-penicillamine hydrochloride (C5H12CINO2S 2219-30-9) see D-Penicillamine DL-penicillamine hydrochloride (CjH,2C1N02S 22572-05-0) see D-Penicillamine penicillin G... 

Evans, P.H. (1977). Serum sulphydryl changes in rheumatoid coalworkers pneumoconiosis patients treated with D-penicillamine. Proc. Roy. Soc. Med. 70, (S3), 95-97. 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

L-cysteine, L-methionine, and D-penicillamine, have been prepared... 

Penicillamine is the United States-adopted name for (d)-penicillamine. 

The titration curve of penicillamine hydrochloride at 25 °C revealed the presence of three ionizable groups with pKa values of 1.8 (carboxyl group), 7.9 (oc-amino group), and 10.5 (/J-thiol group). Recently, the ionization constants for the acidic functions of (D)-penicillamine were verified by pH titration at 37 °C and 0.15 M ionic strength [2], A 1% solution in water has a pH of 4.5-5.5 [3],... 

The enantiomers of this drug differ in their efficacy and activity, with (D)-penicilla-mine being the enantiomer required for pharmaceutical preparations. The (l)-enantiomer is toxic, and its absorption by the human body is more than the (D)-enantiomer. While both enantiomers of penicillamine are desulfhydrated by (r.)-cysteine desulfhydrase, only the (l)-isomer inhibits the action of this enzyme [2], The reported optical rotation values for (D)-penicillamine are ... 

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