The Influence on the Formation of Unstable Haemoglobin by the Immunomodulating 2-Cyanaziridines Azimexone and Bm 41.332 in Mice

Isert, B.; Mengel, Klaus; Bicker, U.; Friedberg, K. D.

doi:10.3109/08923978509047632

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Animal studies showed only a specific toxic reaction of ciamexon with hemoglobin, leading t o its instability and to the formation of Heinz bodies in the red blood cells of treated mice (23) and an increased, dose-dependent susceptibllity t o toxic hemoglobinopathies in rats and dogs (2.3). Thus, our study substantiates the influence of ciamexon on the clinical features and the immunocellular response in RA, but it also demonstrates the agent's potential toxicity.…”

Section: Discussionmentioning

confidence: 99%

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis

Baerwald¹,

Goebel²,

Krause³

et al. 1990

Arthritis & Rheumatism

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To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6-month, prospective, double-blind, placebo-controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose-dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05).The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CDS-positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.Ciamexon is a 2-cyanoaziridine derivative that, in preliminary investigations. has been shown to in-

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Section: Discussionmentioning

confidence: 99%

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis

Baerwald¹,

Goebel²,

Krause³

et al. 1990

Arthritis & Rheumatism

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show abstract

“…), with the Correspondence: Dr B. K. Park, Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX formation of Heinz bodies (Isert et al, 1985;1987).…”

Section: Introductionmentioning

confidence: 99%

“…In the rat, [14C]-ciamexon (Isert et al, 1987) and a related compound, azimexone (Wolfel et al, 1981) are cleared rapidly from plasma. The aziridine ring is reactive toward sulphur nucleophiles such as cysteine (Bicker, 1984) and cellular glutathione (Hata et al, 1988) formation of Heinz bodies (Isert et al, 1985;1987).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of ciamexon by human liver microsomes: an investigation into the formation of stable, chemically reactive and cytotoxic metabolites.

Tingle

Park

1990

Brit J Clinical Pharma

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2 Human livers were obtained from renal transplant donors. All 16 livers investigated metabolized ciamexon in a NADPH-dependent reaction, the major metabolite being the 6-hydroxy-methyl derivative. The hydroxylase activity of the livers varied from 34-577 pmol mg-' min-, with a mean activity of 306 ± 156 pmol mg-' min-'. The further oxidation product, 6-carboxy ciamexon, was also detected in some incubations. A third, unidentified, polar metabolite was present in all incubations (3.34-11.11% of incubated radioactivity). 3 Only very low levels (< 1%) of radioactivity became irreversibly bound to microsomal protein, which suggests that ciamexon undergoes little or no oxidative bioactivation in vitro.4 Human liver microsomes did not metabolize ciamexon to a cytotoxic species, whereas microsomes prepared from mouse livers did generate a cytotoxic species. The degree of toxicity was enhanced if animals were pre-treated with either phenobarbitone or 1B-naphthoflavone.

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Ciamexone, a highly selective immunomodulator — A tool for autoimmune diseases?

Bicker

Usadel

1986

Klin Wochenschr

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Both organ-specific diseases such as insulin dependent diabetes mellitus as well as non organ-specific disorders such as rheumatoid arthritis are thought to be autoimmune in origin. Both T-cell and B-cell mediated immune responses are involved in these diseases. More or less specific immunosuppressants are therefore widely used drugs in the treatment of autoimmune diseases which, however, suppress the immune reactions not only against autoantigens but also against foreign antigens. Cyclosporine (Cyclosporin A) has been a tremendous step forward in a more specific direction but it creates problems in the long term treatment of autoimmune diseases due to the impairment of immune reactions against foreign antigens as well as to compound specific side effects. Ciamexone, a new highly selective immunomodulator, might be an interesting new approach in the treatment of autoimmune diseases. The compound has had effect in different experimental autoimmune situations such as the diabetic BB-rat and experimentally-induced arthritis in mice or rats. The compound does not show antiproliferative activity on T-lymphocytes or B-lymphocytes. The immune response against foreign antigens, e.g. foreign major histocompatibility complex, viral or fungal antigens is not impaired. On the other hand, however, Ciamexone suppresses the antibody production in different animal systems. It is likely that Ciamexone exhibits its immunosuppressive property via the induction of regulating mechanisms. Due to its remarkably good tolerance, Ciamexone has been used in first pilot trials in different human autoimmune situations such as rheumatoid arthritis and insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Influence on the Formation of Unstable Haemoglobin by the Immunomodulating 2-Cyanaziridines Azimexone and Bm 41.332 in Mice

Cited by 5 publications

References 14 publications

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis

Metabolism of ciamexon by human liver microsomes: an investigation into the formation of stable, chemically reactive and cytotoxic metabolites.

Ciamexone, a highly selective immunomodulator — A tool for autoimmune diseases?

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