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At least 19 recordsLinked to original sources
PubMed1976

Studies on the formation of cyclohexylamine and N-methylcyclohexylamine from bromhexine in animals and man, and simultaneous determination of cyclohexylamine and N-methylcyclohexylamine by gas chromatography.

In order to detect cyclohexylamine and N-methylcyclohexylamine simultaneously in urine, a gas chromatographic method was developed in which Chromosorb 103 (porous polymer) was found to be suitable as the column packing. The detection limits were 0.1 mug/ml of cyclohexylamine and 0.4 mug/ml of N-methylcyclohexylamine in urine. In tests on animals administered bromhexine, which contains N-methylcyclohexylamine as part of its side-chain, neither cyclohexylamine nor N-methylcyclohexylamine was detected in the urine.

Animals↗
PubMed1999

Purification and characterization of a novel cyclohexylamine oxidase from the cyclohexylamine-degrading Brevibacterium oxydans IH-35A.

Cyclohexylamine oxidase (CHAO) from a cell extract of Brevibacterium grown on cyclohexylamine was purified 50.2-fold, to electrophoretic homogeneity, by serial chromatographies. The molecular mass of the native enzyme was estimated to be approximately 50 kDa by gel filtration and SDS-PAGE. The optimum pH was 7.4 and the stable pH range was 6.0 to 7.0. The enzyme was thermostable up to 30 degrees C. The enzyme was found to be highly specific for the deamination of alicyclic monoamines such as cyclopentylamine, cycloheptylamine, and N-methylcyclohexylamine and aliphatic monoamines, such as sec-butylamine. The apparent K(m) value for cyclohexylamine was 1.23 mM. The enzyme was inhibited by flavin enzyme inhibitors such as quinine and quinacrine. The N-terminal 27 amino acid residues were determined as Gly-Ser-Val-Thr-Pro-Asp-Pro-Asp-Val-Asp-Val-Ile-Ile-His-Gly-Ala-Gly-Ile-Ser-Gly-Ser-Ala-Ala-Ala-Lys-Ala-Leu-, revealing homology to conventional flavin-containing amine oxidases (EC 1.4.3.4).

Journal Article↗
PubMed1992

The metabolism of cyclamate to cyclohexylamine and its cardiovascular consequences in human volunteers.

A group of 194 diabetic patients were given calcium cyclamate (1 g/day as cyclamic acid equivalents) for a period of 7 days. Blood and urine samples were collected to determine the formation of cyclohexylamine, which is an indirectly acting sympathomimetic amine. Blood pressure and heart rate were recorded before and after treatment. Urine samples were collected each day and analyzed for cyclamate (to check compliance) and cyclohexylamine (to monitor the development of metabolizing activity). After 7 days intake most individuals (78%) did not excrete significant amounts of cyclohexylamine (less than 0.1% of the daily dose of cyclamate) but a small number (8; 4% of the group) excreted more than 20% of the daily dose as cyclohexylamine in the urine. Similar interindividual variations were found in the plasma concentrations of cyclohexylamine after 7 days intake of cyclamate, with 8 individuals having concentrations of 300-1942 ng/ml. The changes in cardiovascular parameters in these 8 subjects between pre- and postdosing were similar to those found in 150 subjects with plasma cyclohexylamine concentrations less than 10 ng/ml. Twenty of the subjects were restudied after receiving calcium cyclamate for 2 weeks at a daily dose equivalent to 2 g of cyclamic acid (0.66 g tds). 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. Twelve patients had plasma concentrations of cyclohexylamine greater than 10 ng/ml (89-2043 ng/ml) at the start of the dose-interval investigations. There were no transient increases or decreases in plasma concentrations of cyclohexylamine which might have resulted in a transient change in blood pressure or heart rate. 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.

Adult↗
PubMed1983

Studies of saccharin and cyclohexylamine in a coupled microsomal activating/embryo culture system.

Rat embryos undergoing organogenesis (day 10.5 of pregnancy) were exposed to 1.0 mM-saccharin or 0.1, 0.3 or 1.0 mM-cyclohexylamine in an in vitro metabolic activating/embryo culture system. Either in the absence or presence of a metabolic activating system, 1.0 mM-saccharin had few adverse effects on yolk-sac growth or embryo growth or differentiation. However, rat embryos cultured in vitro with cyclohexylamine and an adult rat hepatic microsomal activating system showed more growth retardation and dysmorphogenicity than embryos exposed to the same concentrations of cyclohexylamine alone. A concentration of 1.0 mM-cyclohexylamine alone reduced yolk-sac DNA content (by 51%), embryo DNA content (69%) and crown-rump length (26%). 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%). The effects of the metabolic activating system and of cyclohexylamine were additive. Other than decreasing final embryo DNA content, exposure to 0.1 and 0.3 mM-cyclohexylamine did not produce any deleterious effects on in vitro rat embryo growth or differentiation. Thus a substantial concentration of saccharin (1.0 mM) or cyclohexylamine (0.3 mM) in vitro did not elicit markedly deleterious effects on rat organogenesis, a result in keeping with published in vivo findings.

Animals↗
PubMed1989

The pharmacokinetics and tissue concentrations of cyclohexylamine in rats and mice.

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. Cyclohexylamine was absorbed and eliminated more rapidly by mice. Saturation of cyclohexylamine uptake by rat renal cortical slices in vitro and of renal tubular secretion in vivo occurred at concentrations and doses comparable to the oral dose studies. During chronic dietary administration the concentrations of cyclohexylamine in the plasma and testes showed a pronounced diurnal variation in rats which was not detected in mice. The steady-state plasma clearance in rats was approximately one-half that in mice. The concentrations of cyclohexylamine in the plasma and testes of rats, but not mice, showed a nonlinear relationship to dietary intake. Elevated concentrations were found at intakes greater than 200 mg/kg/day. The pharmacokinetics of cyclohexylamine make an important contribution to the difference in sensitivity to testicular atrophy in rats and mice and the dose-response relationship for this toxicity in rats.

Animals↗
PubMed1981

Relation of conformation to antitumor activity of platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388.

The antitumor activity of various platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388 was evaluated by means of the platinum analogue study protocol recommended by the National Cancer Institute. For the former complexes, trans isomers are more efficacious than the corresponding cis isomers. For the latter complexes, cis isomers seem to be somewhat more active than trans isomers. 2-(Aminomethyl)cyclohexylamine platinum complexes exhibited higher activity than 1,2-cyclohexanediamine complexes in this tumor system. These findings encouraged us to determine the structural differences between 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine complexes. Their structures of platinum complexes were elucidated from circular dichroism and 13C NMR spectral analyses, and it has been concluded that the cyclohexane ring of cis-1,2-cyclohexanediamine is nearly perpendicular to the chelate ring, while both rings of trans-1,2-cyclohexanediamine and trans-2-(aminomethyl)cyclohexylamine complexes lie in a common plane. The structure of cis-2-(aminomethyl)cyclohexylamine complexes is flexible, and the cyclohexane ring is not perpendicular to the chelate ring. The coplanarity of trans isomers and the flexibility of cis-2-(aminomethyl)cyclohexylamine complexes allow them easy approach to the target DNA. However, the perpendicular ring of cis-1,2-cyclohexanediamine complexes would prevent their interactions with dna molecules due to the steric hindrance.

Animals↗
PubMed1989

The metabolism and testicular toxicity of cyclohexylamine in rats and mice during chronic dietary administration.

Cyclohexylamine hydrochloride has been given in the diet to mice and to Wistar and DA rats for 13 weeks, to provide a constant intake of 400 mg of the base/kg/day. Significantly decreased food intake and body weight gain were found in both strains of rats but not mice. The metabolism of [14C]cyclohexylamine was widely different in Wistar and DA rats and in rats and mice, and these differences were not altered appreciably by chronic intake for 13 weeks. The differences in metabolism resulted in marked and persistent differences in the concentrations of the hydroxylated metabolites in the plasma and testes of treated animals with Wistar much greater than DA much greater than mice. 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. DA rats appeared more sensitive to testicular toxicity from cyclohexylamine than Wistar rats, while mice showed no evidence of testicular damage. These data show that the development of testicular toxicity is not related to the extent of hydroxylation. The concentrations of cyclohexylamine in the plasma and testes of the treated animals were lower in mice than in either strain of rats despite a similar daily intake. This suggests that species differences in pharmacokinetics may contribute to the apparent difference in sensitivity to testicular toxicity.

Animals↗
PubMed1992

Blood pressure changes and sympathetic function in rats given cyclohexylamine by intravenous infusion.

Intravenous infusion of cyclohexylamine (30-120 mg/kg) caused a dose-dependent increase in blood pressure in urethane-anesthetized rats. The increase in blood pressure was inversely related to the duration of the infusion. The blood pressure returned to baseline values (+/- 5 mm Hg) within 60 min of the end of the infusion after doses of 30 and 60 mg/kg were administered over 20 and 40 min. The plasma concentrations of cyclohexylamine were related linearly to the administered dose and decreased only 27% between the end of the infusion and 60 min later. The concentration-effect relationship showed clockwise hysteresis, indicative of tachyphylaxis, as has been reported in humans (Eichelbaum et al., 1974). Administration of bolus doses of tyramine at the end of the infusion or 60 min later demonstrated the presence of an indirect sympathomimetic response, although this was attenuated to a greater extent by high doses and more rapid infusions of cyclohexylamine. An almost complete loss of response to tyramine was found only in animals given 120 mg/kg over 40 min. The presence of a tyramine response 60 min after the infusion of 60 mg/kg occurred when there was an essentially complete reversal of the hypertensive effect of cyclohexylamine. These data indicate that the hypertensive effect of the indirectly acting sympathomimetic amine cyclohexylamine occurs primarily during rapid increases in plasma concentrations. Tachyphylaxis develops rapidly after the cessation of the infusion which is probably due largely to reuptake of released noradrenaline at low doses and depletion of releasable noradrenaline at high doses.

Animals↗
PubMed1976

Evaluation of the mutagenic potential of cyclohexylamine on spermatogonia of the Chinese hamster.

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. Each test group comprised 8 male hamsters selected at random. Approximately 100 metaphases from each animal were assessed. The doses were 5 X 150 mg cyclohexylamine sulphate (approx. 5 X 102 mg base) per kg body-weight orally, and 5 X 100 mg cyclophosphamide per kg body-weight orally. The individual doses were administered at intervals of 24 h. Preparations were made 24 h after the final treatment, essentially by the method of Hoo and Bowles [10]. Gaps, breaks, fragments, deletions and translocations were assessed as structural changes; frequencies were determined of the metaphases (a) with aberration(s) including gaps, (b)with aberration(s) less gaps and (c)with translocation(s). Aberrations occurred in the untreated negative control group (1.24% incl. gaps, 0.25% without gaps). Translocations were not seen in the untreated group. In the cyclochexylamine group, the frequencies of the aberrant metaphases were sometimes less than in the control group (0.87% including gaps, 0.37% without gaps). Statistically, the results were not significantly different from the control data. No translocations were seen after administration of cyclohexylamine. The positive cyclophosphamide control group clearly differed from the untreated control and from the cyclohexylamine group in the parameters (a) to (c); mainly, the results were highly significantly different from those obtained in the untreated control group. The frequencies of the aberrant metaphases were 3.41% including gaps and 1.99% without gaps. The frequency of the translocations was 0.71% (5 out of 704). Cyclohexylamine sulphate, administered 5 times at 150 mg/kg body-weight orally, had no mutagenic effect, whereas cyclophosphamide, adminstered 5 times at 100 mg/kg body-weight orally, had a chromosome-damaging effect on Chinese hamster spermatogonia.

Animals↗
PubMed1995

Cyclohexylamine inhibits the adhesion of lymphocytic cells to human syncytiotrophoblast.

We have previously shown that lymphocytic cells adhere to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). During the course of studies aimed at investigating the role of cell surface carbohydrates in adhesion, it was discovered that a contaminant of commercial fucose-1-phosphate, dicyclohexylamine, inhibited MOLT-trophoblast adhesion. Dicyclohexylamine and the related compounds, cyclohexylamine and hexylamine, inhibited adhesion in a dose-responsive manner with half-maximal inhibition seen at about 4 mM. While the pressor effects of cyclohexylamine, the principal metabolite of cyclamate, are well known, this is the first report of an effect of this and related compounds on cell adhesion activity. The inhibitory effect was reversible and, at concentrations less than 25 mM, did not result in loss of cell viability. Several possible mechanisms of action of cyclohexylamine were examined in an attempt to explain the effect on adhesion. No evidence was found to suggest that the effects of cyclohexylamine were due to inhibition of polyamine synthesis, increase in intracellular Ca2+ concentration or to a lysosomotropic effect. The concentrations of cyclohexylamine used are within the range of plasma concentrations attainable in humans, raising the possibility that the in vitro effects described here may also occur in vivo. The results also suggest that caution should be used in the interpretation of results obtained from experiments where cell adhesion is blocked using exogenous monosaccharides that are in the form of dicyclohexylammonium salts. Appropriate controls must be included or, if possible, sodium, potassium or barium salts should be chosen.

Cell Adhesion↗
PubMed2002

2.4-A crystal structure of the asymmetric platinum complex [Pt(ammine)(cyclohexylamine)]2+ bound to a dodecamer DNA duplex.

cis-trans-cis-Ammine(cyclohexylamine)diacetatodichloroplatinum(IV) is an oral analog of the platinum anti-cancer drug cisplatin that is currently in phase III clinical trials. Its active form, [Pt(ammine)(cyclohexylamine)]2+, binds to DNA similarly to cisplatin, forming intra- and interstrand cross-links between adjacent purine bases. Since [Pt(ammine)(cyclohexylamine)]2+ contains two different ligands, it can form two isomeric 1,2-d(GpG) intrastrand cross-links. Here we report the 2.4-A resolution x-ray crystal structure of the major adduct between [Pt(ammine)(cyclohexylamine)]2+ and a DNA dodecamer, using the same sequence as previously reported for crystal structures of cisplatin-DNA (Takahara, P. M., Rosenzweig, A. C., Frederick, C. A., and Lippard, S. J. (1995) Nature 377, 649-652) and oxaliplatin-DNA (Spingler, B., Whittington, D. A., and Lippard, S. J. (2001) Inorg. Chem. 40, 5596-5602). Both duplexes in the asymmetric unit contain 1,2-intrastrand cross-links in which the cyclohexylamine ligand is directed toward the 3'-end of the platinated strand. The chair conformation of the cyclohexyl group is clearly resolved. Platination distorts the duplex, resulting in a global bend angle of about 38(o) and a dihedral angle between platinated guanine bases of approximately 31(o). Both end-to-end and end-to-groove packing interactions occur in the crystal lattice, the latter positioned in the minor groove across from the site of the platinum cross-link. A high degree of homology observed between this structure and the previously reported platinum-DNA structures suggests that these platinum complexes distort the DNA duplex in a very similar manner. These results suggest that differences in activity between these drugs are unlikely to result from gross conformational distortions in DNA structure following platinum intrastrand cross-link formation.

Chromatography, High Pressure Liquid↗
PubMed2003

Cyclamate intake and cyclohexylamine excretion are not related to male fertility in humans.

Cyclamate and its metabolite cyclohexylamine affect male fertility in high dose animal studies, but this affect has not been investigated in epidemiological studies. This paper reports the first epidemiological study designed to investigate the possibility of a relationship between cyclamate and cyclohexylamine and male fertility in humans, in which 405 cases of clinically defined infertility in men and 379 controls were surveyed. Semen evaluation, urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were compared between cases and controls. 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. The lack of association remained after adjusting by age, area of residence, education, total energy intake and other variables. No significant correlations were observed between cyclamate intake, metabolism or excretion, and sperm count and motility. The results demonstrate no effect of cyclamate or cyclohexylamine on male fertility at the present levels of cyclamate consumption.

Adult↗
PubMed1977

Purification and some properties of cyclohexylamine oxidase from a Pseudomonas sp.

Cyclohexylamine oxidase was purified 90-fold from cell-free extracts of Pseudomonas sp. capable of assimilating sodium cyclamate. The purified enzyme was homogeneous in disc electrophoresis, and the molecular weight was found to be approximately 80,000 by gel filtration. The enzyme catalyzed the following reaction: cyclohexylamine+O2+H2O leads to cyclohexanone+NH3+H2O2. The enzyme thus can be classified as an amine oxidase; it utilized oxygen as the ultimate electron acceptor. The pH optimum of the reaction was 6.8 and the apparent Km value for cyclohexylamine was 2.5 X 10(-4) M. The enzyme was highly specific for the deamination of alicyclic primary amines such as cyclohexylamine, but was found to be inactive toward ordinary amines used as substrates for amine oxidases. The enzyme solution was yellow in color and showed a typical flavoprotein spectrum; the addition of cyclohexylamine under anaerobic conditions caused reduction of the flavin in the native enzyme. The flavin of the prosthetic group was identified as FAD by thin layer chromatography. The participation of sulfhydryl groups in the enzymic action was also suggested by the observation that the enzyme activity was inhibited in the presence of PCMB and could be recovered by the addition of glutathione.

Amines↗
PubMed1975

[Influence of several weeks' treatment of male and female mice with saccharin, cyclamate or cyclohexylamine sulfate on fertility and dominant lethal effects (author's transl)].

The purpose of this investigation was to find out whether long-term treatment of male and female mice with saccharin sodium, sodium cyclamate or cyclohexylamine sulfate, would reduce fertility or induce dominant lethal mutations. Before mating, saccharin sodium or sodium cyclamate were added to the food in a concentration of 1%, while cyclohexylamine sulfate was added in a concentration of 0.11% for at least 10 weeks. This treatment corresponded, in the case of saccharin sodium and sodium cyclamate, to an active substance intake of approx. 2000 mg/kg per day and for cyclohexylamine sulfate to an intake of approx. 200 mg/kg per day (corresponding to approx. 136 mg cyclohexylamine per kilogram per day). These doses affected neither the females nor the males in respect of appearance, behaviour, and weight gain. The doses were also compatible with the normal fertility of the animals. Furthermore, in all cases the treatment did not cause a biologically important increase of pre-implantative and post-implantative losses. The dominant lethal tests did not indicate a mutagenic action of saccharin sodium or sodium cyclamate (1% in the food) and of cyclohexylamine sulfate (0.11% in the food) after 10 weeks' treatment of male and female mice. These results, obtained after long-term treatment, corresponded generally to the findin

Animals↗
PubMed1989

Assessment of the genotoxicity of calcium cyclamate and cyclohexylamine.

Calcium cyclamate and its major metabolite cyclohexylamine have been subjected to numerous evaluations for genetic activity. With the exception of studies for chromosome damage, the results have been negative. Results from a wide range of in vitro and in vivo cytogenetic assays ranged from clearly negative to various degrees of clastogenicity. Interpretation of the cytogenetic studies has been complicated by the conflicting responses, although some of the positive effects seem to be the consequence of secondary effects produced by high ion levels and excessive toxicity. In the studies presented here calcium cyclamate and cyclohexylamine were tested for mutagenic activity using an in vitro mammalian cells assay for gene mutation and an in vitro unscheduled DNA synthesis assay in rat hepatocytes with the Drosophila sex-linked recessive lethal assay. Calcium cyclamate was not genetically active in any of the three assays when tested to the maximum possible concentrations. The compound was largely nontoxic but did show some evidence of cytotoxicity in rat hepatocytes at concentrations of 1 mg/ml and higher. Cyclohexylamine was also negative in the three assays, but was considerably more cytotoxic at the concentrations used. 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.

Animals↗