Disease relevance of CYCLOHEXYLAMINE

• This review of the published and unpublished literature on cyclamate attempts to evaluate the carcinogenicity question and other important aspects of the toxicity of cyclamate and cyclohexylamine, including their effects on various organ systems, their genotoxic potential, and their effects on reproduction [1].
• Biodegradation of cyclohexylamine by Brevibacterium oxydans IH-35A [2].
• Male Wistar strain rats were fed a diet providing an intake of 0 or 400 mg cyclohexylamine (CHA)/kg body weight/day for 1, 3, 7, 9, or 13 weeks [3].
• Purification and some properties of cyclohexylamine oxidase from a Pseudomonas sp [4].
• No evidence was found of a significant association between cyclamate intake and male infertility; neither high cyclamate nor high cyclohexylamine excretion were associated with elevated risk [5].

High impact information on CYCLOHEXYLAMINE

• This modification combined with replacement of the minimal sequence isoleucine residue by 1-aminocyclohexane carboxylic acid to stabilize the beta-turn conformation required for recognition by the Grb2-SH2 domain resulted in the high affinity (47 nM in an ELISA assay) and selective phosphopeptide Ac-pTyr-Ac6c-Asn-NH(3-naphthalen-1-yl-propyl) [6].
• It was further demonstrated that the efficiencies of these cyclization protocols could be enhanced by the presence of cyclohexylamine [7].
• Female rats were dosed orally with one-fifth the LD50 of either 1-nitrosopiperidine (a carcinogen), cyclohexylamine, piperidine, 4-carboxy-1-nitrosopiperidine, 4-cyclohexyl-1-nitrosopiperidine or 2,6-dimethyl-1-nitrosopiperidine at 21 and 4 hr before they were killed [8].
• Oxidative deamination of cyclohexylamine and its homologs by rabbit liver microsomes [9].
• In the presence of L-alpha-difluoromethyl ornithine (an inhibitor of ODC) or cyclohexylamine (an inhibitor of spermidine synthase) development of porcine parthenotes decreased, apoptosis increased, and mRNA expression of the ratio of Bak/Bcl-xL and Fas/Bcl-xL, and caspase 3 increased [10].

Chemical compound and disease context of CYCLOHEXYLAMINE

• We have shown that the introduction of amino acid moieties and the replacement of cyclohexylamine with nitroxyl moiety leads to a faster decomposition, higher alkylating, lower carbamoylating activity, better antimelanomic activity and lower general toxicity, when compared to those of CCNU [11].
• Long term toxicity and reproduction study (including a teratogenicity study) with cyclamate, saccharin and cyclohexylamine [12].

Biological context of CYCLOHEXYLAMINE

• Plasma concentrations of cyclohexylamine, heart rate, and blood pressure were measured every 30 min for a period of 8 hr (one dose interval) after the final dose [13].
• These data indicate that the metabolism of cyclamate (2 g/day) to cyclohexylamine would not affect blood pressure or heart rate even in individuals with high metabolizing ability [13].
• The pharmacokinetics and tissue concentrations of cyclohexylamine in rats and mice [14].
• Cyclohexylamine showed dose-dependent kinetics after administration of single oral doses up to 500 mg/kg in rats, with a reduction in plasma clearance, an increase in apparent half-life, and an increased area under the testicular concentration-time curve [14].
• The results from the three studies conducted in this evaluation are in general agreement with the majority of published genetic toxicology data for these two chemicals and indicated that the calcium cyclamate and cyclohexylamine have no direct, intrinsic genotoxicity of the type measured by these assays [15].

Anatomical context of CYCLOHEXYLAMINE

• Evaluation of the mutagenic potential of cyclohexylamine on spermatogonia of the Chinese hamster [16].
• The unconfirmed clastogenic effect of CHA was restricted to rats, but it occurred in both bone marrow and spermatogonia [17].
• Semen evaluation, urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were compared between cases and controls [5].
• In the presence of a hepatic microsomal activating system this same dose of cyclohexylamine decreased yolk-sac DNA (60%), embryo DNA (84%) and crown-rump length (49%) [18].
• Cyclohexylamine inhibits the adhesion of lymphocytic cells to human syncytiotrophoblast [19].

Associations of CYCLOHEXYLAMINE with other chemical compounds

• Quantification of cyclamate and cyclohexylamine in urine samples using high-performance liquid chromatography with trinitrobenzenesulfonic acid pre-column derivatization [20].
• Thus, the presence of one ammine and one cyclohexylamine carrier ligand in the mixed amine complex, as opposed to the diammine ligands in cisplatin, leads to an increase in drug distribution and an alteration in the kinetics of tissue binding and removal of platinum [21].
• Delta 5.7-Sterol delta 7-reductase was inhibited by both RPR 101821, a protonated cyclohexylamine, and BM 15.766, a piperazine derivative, with IC50 values of 1 microM [22].
• In a cytogenetic study on the spermatogonia of Chinese hamster, cyclohexylamine (neutral sulphate) was evaluated for mutagenic effects in comparison with an untreated control group and a group treated with the mutagenic compound cyclophosphamide, by assessing spermatogonial metaphases of treated Chinese hamster for chromosomal structural changes [16].
• Uptake of [3H]GABA into cell cultures of rat cerebellum and olfactory bulb was studied by autoradiography, using beta-alanine and aminocyclohexane carboxylic acid to distinguish neuronal-specific and glial-specific uptake [23].

Gene context of CYCLOHEXYLAMINE

• These results suggest that cyclohexylamine specifically interacts with the binding of CD23 and IgE [24].
• The concentrations of cyclohexylamine in the plasma and testes of rats, but not mice, showed a nonlinear relationship to dietary intake [14].
• 2-Cyclohexylamino-2-demethoxy-hypocrellin B (CHAHB) is a new photosensitizer synthesized by the mild reaction between hypocrellin B (HB) and cyclohexylamine, in which the peri-hydroxylated perylenequinone structure of the parent HB is preserved and the photoresponse is enhanced markedly [25].
• However, addition of a spermidine synthase inhibitor, cyclohexylamine, at 150 or 250 microg per plant (each dose was applied two times in total at an interval of 4 days) significantly reduced flower primordium counts, indicating that spermidine is involved in floral initiation and floral development in P. tuberosa [26].
• By using 13C MAS NMR it was shown that the occluded template (cyclohexylamine) is present as ions [27].

Analytical, diagnostic and therapeutic context of CYCLOHEXYLAMINE

• Since that time, the carcinogenic potential of cyclamate and cyclohexylamine, its principal metabolite, has been reevaluated in a group of well-controlled, well-designed bioassays that have failed to substantiate the earlier findings [1].
• JM216 (bis-acetato ammine dichloro cyclohexylamine Pt IV) is an oral platinum complex presently undergoing phase II clinical trials [28].
• The metabolism of cyclamate to cyclohexylamine and its cardiovascular consequences in human volunteers [13].
• After 7 and 13 weeks testicular atrophy was demonstrated in both strains of rats given cyclohexylamine diet by a decrease in organ weight and by histological changes [29].
• An HPLC isocratic method with pre-column derivatization and UV detection for the quantification of cyclamate and cyclohexylamine in urine samples is described [20].

References