7. Allyl Amine
13. Nsc 7600
14. Ccris 4746
15. Hsdb 2065
17. Einecs 203-463-9
19. Brn 0635703
24. Allylamine, Polymers
25. Allylamine Homopolymer
27. 2-propenamine Homopolymer
28. Paa 1lv
30. Paa 10c
31. Paa 10l
35. 2-propenyl Amine
37. Allylamine, 98%
42. Allylamine, >=99%
46. Allylamine, 98% 25ml
47. 4-04-00-01057 (beilstein Handbook Reference)
48. Wln: Z2u1
51. 2-propen-1-amine, Homopolymer
56. Allylamine [un2334] [poison]
58. 71550-12-4 (hydrochloride)
60. Allylamine [un2334] [poison]
67. Allylamine, Purum, >=98.0% (gc)
70. Un 2334
71. Allylamine, Puriss., >=99.5% (gc)
95. Poly(allylamine Hydrochloride), Mw ~ 120,000-200,000 10g
|Molecular Weight||57.096 g/mol|
|Hydrogen Bond Donor Count||1|
|Hydrogen Bond Acceptor Count||1|
|Rotatable Bond Count||1|
|Exact Mass||57.058 g/mol|
|Monoisotopic Mass||57.058 g/mol|
|Topological Polar Surface Area||26 A^2|
|Heavy Atom Count||4|
|Isotope Atom Count||0|
|Defined Atom Stereocenter Count||0|
|Undefined Atom Stereocenter Count||0|
|Defined Bond Stereocenter Count||0|
|Undefined Bond Stereocenter Count||0|
|Covalently Bonded Unit Count||1|
/Investigators/studied the uptake, tissue distribution, toxicokinetics, and excretion of allylamine by giving rats (14)C-allylamine (1.5 uCi/kg; 150 mg/kg) by gavage. Rats were killed at intervals up to 2 h, and multiple tissues were sampled. Aorta showed the highest counts of (14)C-label at most times (5-10-fold higher than most other organs, 100-fold higher than blood), although a minority of aortas had very low counts. Coronary arteries dissected from the hearts showed consistently higher (14)C-label than myocardium. Liver counts, which were high at 5 min, decreased rapidly; kidney counts slowly increased until 45 min, then decreased rapidly, consistent with an excretory function for this organ. Counts of (14)C-label were lower in all other organs, including lung, skeletal muscle, brain, testes, pancreas, adrenal, spleen, fat, and blood. Toxicokinetic study showed a very rapid absorption rate and short half-lives (less than 1 h) for those organs which reasonably fit a toxicokinetic one-compartment model. (14)C-label was rapidly excreted in the urine; approximately 60% of the dose given was recovered by 24 h. No counts were found in feces. These studies indicate that allylamine--or its metabolite(s)--has a unique predilection for elastic and muscular arteries, such as aorta and coronary arteries. This relatively specific cardiovascular toxin acts as a highly polar, highly water soluble substance, which is rapidly absorbed from the gastrointestinal tract, has a short half-life in most tissues, and is rapidly excreted in the urine. ...
Boor PJ; Toxicology 35 (3): 167-77 (1985)
...Allylamine, a known cardiovascular toxin, is metabolized in vitro to acrolein, /and/ has been hypothesized to act as a distal toxin. In this study, 3-hydroxypropylmercapturic acid was isolated and identified by MS, NMR, and 2D-NMR spectroscopy as the sole urinary metabolite of allylamine metabolism in vivo. Parallel experiments showed reduced glutathione (GSH) depletion in several organs (most marked in aorta, blood, and lung), which is consistent with GSH conjugation of the proposed acrolein intermediate. These findings indicate that allylamine was metabolized in vivo to a highly reactive aldehyde which was converted to a mercapturic acid through a GSH conjugation pathway. ...
Boor PJ et al; Biochem Pharmacol 36 (24): 4347-53 (1987)
Acrolein was detected in homogenates of rat aorta, lung, skeletal muscle and heart incubated with allylamine. ... Hydrogen peroxide, a product of oxidative deamination, was generated during allylamine oxidation. Acrolein was also produced by bovine plasma amine oxidase & porcine kidney diamine oxidase but not by rat liver or brain homogenates. ... Allylamine competitively inhibited benzylamine oxidation in rat aorta, but pargyline-sensitive monoamine oxidase was not involved in acrolein production. The high activity in aorta, the competition with benzylamine, and the sensitivity to benzylamine oxidase inhibitors indicate that benzylamine oxidase is the active enzyme in oxidizing allylamine. ...
NELSON TJ, BOOR PJ; BIOCHEM PHARMACOL 31 (4): 509 (1982)
Aortic smooth muscle cells (SMC) modulate from a contractile to a proliferative phenotype upon subchronic exposure to allylamine. The present studies were designed to determine if this phenotypic modulation is associated with alterations in the metabolism of membrane phosphoinositides. (32)P incorporation into phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA) was lower by 31, 35, and 22%, respectively, in SMC from allylamine-treated animals relative to controls. In contrast, incorporation of (3)H-myoinositol into inositol phosphates did not differ in allylamine cells relative to control cells. Exposure to dibutyryl (db) cAMP (0.2 mM) and theophylline (0.1 mM) reduced (32)P incorporation into PIP and PIP2 in SMC from both experimental groups. Under these conditions, a decrease in (3)H-myoinositol incorporation into inositol 1-phosphate was only observed in allylamine cells. The effects of db cAMP and theophylline in allylamine and control SMC correlated with a marked decrease in cellular proliferation. These results suggest that alterations in phosphoinositide synthesis and/or degradation contribute to the enhanced proliferation of SMC induced by allylamine. To further examine this concept, the effects of agents which modulate protein kinase C (PKC) activity were evaluated. Sphingosine (125-500 ng/mL), a PKC inhibitor, decreased SMC proliferation in allylamine, but not control cells. 12-O-Tetradecanoylphorbol-13-acetate (1-100 ng/mL), a PKC agonist, stimulated proliferation in control cells, but inhibited proliferation in cells from allylamine-treated animals. /The authors/ conclude that allylamine-induced phenotypic modulation of SMC is associated with alterations in phosphoinositide metabolism.
Cox LR et al; Exp Mol Pathol Aug; 53 (1): 52-63 (1990)
Allylamine (3-aminopropene) is a specific cardiac toxicant that causes aortic, valvular and myocardial lesions in many species. Myocardial necrosis can be observed 24 h after a single dose. Acute toxicity is believed to involve metabolism of allylamine to highly reactive acrolein (2-propenal). Allylamine has been shown to bind to mitochondria from aorta and heart, suggesting that the subcellular site of injury is at or near the mitochondrion. The present investigation compared the effect of allylamine and its primary metabolite, acrolein, on electron transport and oxidative phosphorylation in mitochondria isolated from rat heart (RHM). Both compounds weakly inhibited mitochondrial electron transport with either the combination of glutamate, malate, and malonate (GMM, NADH-linked) or succinate as substrate. Comparisons of the slopes of concentration-effect regression (range of concentrations tested, 0.20-2.0 mM) lines showed acrolein to have significantly greater inhibitory effects than allylamine (range of concentrations tested, 0.22-6.4 mM) on GMM oxidation, while no significant difference in the abilities of the compounds to inhibit succinate oxidation were observed, indicating site preferences for inhibitory action. The addition of an uncoupling agent could not reverse inhibition with either substrate system. These results indicate that both the parent compound and its proposed metabolite primarily inhibit electron transport with little direct effect on the coupling mechanism. The State III EC50 (effective concentrations for 50% inhibition of control mitochondrial enzyme activities) for allylamine (2.29 mM with succinate as substrate and 1.22 mM with GMM) and acrolein (0.80 mM with succinate as substrate and 0.39 mM with GMM) are probably too great to invoke the direct action of either the parent compound or its oxidized metabolite on mitochondrial electron transport as a primary mechanism in the cardiotoxic action of allylamine.
Biagini RE et al; Toxicology 62 (1): 95-106 (1990)
Studies were conducted to evaluate the mechanisms involved in the deregulation of proliferative control induced by allylamine (AAM) in rat aortic smooth muscle cells (SMCs). Subcultured SMCs from animals treated with AAM (70 mg/kg) or tap water for 20 days were processed for measurements of (3)H-thymidine incorporation and c-Ha-ras mRNA levels. Pre-confluent AAM cells stimulated with 10% fetal bovine serum exhibited enhanced mitogenic responsiveness relative to control cells. Decreased (3)H-thymidine incorporation was observed in post-confluent cultures of both cell types relative to pre-confluent counterparts. A 5-fold increase in c-Ha-ras transcript levels was observed in pre-confluent/cycling cultures of AAM cells relative to controls. C-Ha-ras expression was markedly reduced in post-confluent cultures of both cell types as compared to pre-confluent counterparts. No difference between control and AAM cells was observed during G1-synchronization of pre- or post-confluent cultures. These results suggest that the enhanced proliferative capacity induced by AAM is associated with alterations in cell cycle-related expression of the c-Ha-ras protooncogene.
Bowes RC 3rd, Ramos KS; Toxicol Lett 66 (3): 263-72 (1993)
The profile of endogenous protein phosphorylation mediated by protein kinase C (PKC) was examined in cell fractions prepared from subcultured aortic smooth muscle cells (SMCs) isolated from rats treated with 70 mg/kg allylamine (AAM) or tap water for 20 days. Increased phosphorylation of endogenous proteins was observed under unstimulated conditions in the particulate, but not cytosolic, fraction of cells from AAM-treated animals (i.e. AAM cells) relative to control cells. Although the same phosphorylation bands were observed in the particulate or cytosolic fraction of control and AAM cells following phorbol ester stimulation of the enzyme, enhanced PKC-mediated phosphorylation was observed in both fractions of AAM cells relative to control cells. Measurements of exogenous histone Type III-S phosphorylation by PKC following in vitro exposure of naive SMCs to 100 uM AAM for up to 60 min revealed that AAM selectively increased histone phosphorylation in the cytosolic fraction of SMCs. These results demonstrate that AAM treatment enhances PKC-mediated protein phosphorylation in rat aortic SMCs and raise the possibility that such alterations participate in the angiotoxic response to AAM.
Ramos KS, Ou X et al; Toxicol Lett 73 (2): 123-33 (1994)
Chronic oxidative injury by allylamine (AAM) induces proliferative vascular smooth muscle cell (vSMC) phenotypes in the rat aorta similar to those seen in rodent and human atherosclerotic lesions. The proliferative advantage of AAM vSMC compared to control cells is maintained with serial passage of the cells and the advantage is nullified when AAM cells are seeded on a collagen substrate. In this study, /investigators/ evaluate the potential role of cyclin dependent kinase inhibitors, p27 and p21, and mitogen activated protein (MAP) kinases, ERK1/2, in mediating the proliferative advantage of AAM stressed vSMC over control cells on plastic or collagen substrates. p27 levels in randomly cycling cells were comparable in both cell types irrespective of the substrate. In contrast, basal levels of p21 were 1.9 +/- 0.3 (P < 0.05)-fold higher in randomly cycling AAM cells seeded on plastic compared to controls, a difference that was lost on a collagen substrate. Following G0 synchronization, basal levels of both p27 and p21 were higher in AAM cells seeded on plastic compared to controls (1.7 +/- 0.2 and 2.0 +/- 0.3-fold, respectively, P < 0.05), but these differences were lost upon mitogenic stimulation. Pyrrolidine dithiocarbamate (PDTC) decreased p27 and p21 levels in cycling AAM cells relative to controls in a substrate-dependent manner. AAM cells seeded on plastic exhibited enhanced ERK1/2 activation upon mitogenic stimulation; seeding on collagen nullified this advantage. The duration of ERK1/2 activation was prolonged in AAM cells independently of the seeding substrate. /It was concluded/ that substrate-dependent acquisition of proliferative phenotypes following repeated cycles of AAM injury correlates with modulation of the cyclin dependent kinase inhibitors, p27 and p21.
Jones SA et al; J Cell Biochem 91 (6): 1248-59 (2004)
The cardiovascular toxin allylamine (3-aminopropene) has been shown to concentrate in elastic and muscular tissues. In this study the (14)C-moiety of (14)C-allylamine was traced in aortas of adult Sprague-Dawley rats after intravenously injecting 30 uCi of (14)C-allylamine (spec. act. = 0.4 mCi/mM). At 5, 10, 15 and 20 min after injection 33.3-29.8% of the 14C-moiety was sequestered in aortas; at 30 min 16.8% was still present. Subcellular fractionation of the postnuclear supernatant by isopycinic centrifugation in sucrose demonstrated that 5 min after administration of (14)C-allylamine, the (14)C-moiety displayed a modal density peak of 1.20 g/mL. Similar activities were observed up to 30 min exposure. This modal density was similar to the distribution pattern of mitochondria based on analysis of malate dehydrogenase activities. As early as 20 min post-exposure, mitochondrial malate dehydrogenase activities of aortic mitochondria decreased, while cytosolic malate dehydrogenase activities increased, suggesting mitochondrial membrane perturbation. /The authors/ suggest that the subcellular site for allylamine injury to the aorta is the mitochondrion.
Hysmith RM, Boor PJ; Toxicology 35 (3): 179-87 (1985)
Acrolein was detected in homogenates of rat aorta, lung, skeletal muscle, and heart incubated with allylamine. Semicarbazide and hydralazine, which protect against allylamine-induced myocardial injury in vivo in the rat, inhibited acrolein formation. Hydrogen peroxide, a product of oxidative deamination, was generated during allylamine oxidation. Acrolein was also produced from allylamine by bovine plasma amine oxidase and porcine kidney diamine oxidase but not by rat liver or brain homogenates. Allylamine competitively inhibited benzylamine oxidation in rat aorta, but pargyline-sensitive monoamine oxidase was not involved in acrolein production. The high activity in aorta, the competition with benzylamine, and the sensitivity to benzylamine oxidase inhibitors indicate that benzylamine oxidase is the active enzyme in oxidizing allylamine. The formation of acrolein may be the basis of the cardiotoxic action of allylamine.
NELSON TJ, BOOR PJ; BIOCHEM PHARMACOL 31 (4): 509 (1982)
Absorption spectra showed that allylamine formed a complex with pyridoxal phosphate in soln at ph 5.2, 7.4 & 8.0. At 1X10-2 M, allylamine inhibited activity of serum glutamic-oxalacetic transaminase by 22.5%, & at 1X10-4 M it inhibited serum glutamic-pyruvic transaminase by 13.2%. It inhibited activity of serum enzymes in vitro at same concn as isonicotinic acid hydrazide. IV injection of 60 mg/kg into rats decreased activities of hepatic glutamic-oxalacetic transaminase & glutamic-pyruvic transaminase by about 50%, when these levels were determined about 5 min after injection.
KUZUYA F ET AL; J NUTR 93 (3): 280 (1967)
The profile of endogenous protein phosphorylation mediated by protein kinase C (PKC) was examined in cell fractions prepared from subcultured aortic smooth muscle cells (SMCs) isolated from rats treated with 70 mg/kg allylamine (AAM) or tap water for 20 days. Increased phosphorylation of endogenous proteins was observed under unstimulated conditions in the particulate but not cytosolic, fraction of cells from allylamine-treated animals (ie allylamine cells). Although the same phosphorylation bands were observed in the particulate or cytosolic fraction of control and allylamine cells following phorbol ester stimulation of the enzyme, enhancedprotein kinase C-mediated phosphorylation was observed in 60th fractions of allylamine cells. Measurements of exogenous histone Type III-S phosphorylation by protein kinase C followlng in vitro exposure of native smooth muscle cells to 100 uM allylamine for up to 60 min revealed that allylamine selectively increased histone phosphorylation in the cytosolic fraction of SMCs. AAM treatment enhances protein kinase C-mediated protein phosphorylation in rat aortic smooth muscle cells.
Ramos KS, Ou X; Toxicol Lett; 73 (2): 123-33 (1994)
Studies were conducted to evaluate the mechanisms involved in the deregulation of proliferative control induced by allylamine in rat aortic smooth muscle cells. Subcultured smooth muscle cells from animals treated with allylamine (70 mg/kg) for 20 days were processed for measurements of (3)H-thymidine incorporation and c-Ha-ras mRNA levels. Pre-confluent allylamine cells stimulated with 10% fetal bovine serum exhibited enhanced mitogenic responsiveness. Decreased (3)H-thymidine incorporation was observed in post-confluent cultures relative to pre-confluent counterparts. A 5-fold increase in c-Ha-ras transcript levels was observed in pre-confluent/cycling cultures of allylamine cells relative to controls. C-Ha-ras expression was markedly reduced in post-confluent cultures of both cell types as compared to pre-confluent counterparts. No difference between control and allylamine cells was observed during GI-synchronization of pre- or post-confluent cultures. The enhanced proliferative capacity induced by allylamine is associated with alterations in cell cycle-related expression of the c-Ha-ras protooncogene.
Bowes RC 3d, Ramos KS; Toxicol Lett; 66 (3): 263-72 (1993)