Approximately 10% of aspartame (by weight) is broken down into methanol in the small intestine. Most of the methanol is absorbed and quickly converted into formaldehyde. Approximately 50% of aspartame (by weight) is broken down into phenylalanine. Approximately 40% of aspartame (by mass) is broken down into aspartic acid.
Unlike some other intense sweeteners, aspartame is metabolized in the body and consequently has some nutritive value: 1 g provides approx 17 kJ (4 kcal). However, in practice, the small quantity of aspartame consumed provides a minimal nutritive effect.
The use of aspartame has been of some concern owing to the formation of the potentially toxic metabolites methanol, aspartic acid, and phenylalanine. Of these materials, only phenylalanine is produced in sufficient quantities, at normal aspartame intake levels, to cause concern.
Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening agent that organoleptically has about 180 times the sweetness of sugar. The metabolism of aspartame has been studied in mice, rats, rabbits, dogs, monkeys, and humans. The compound was digested in all species in the same way as are natural constituents of the diet. Hydrolysis of the methyl group by intestinal esterases yielded methanol, which was oxidized in the one-carbon metabolic pool to CO2. The resultant dipeptide was split at the mucosal surface by dipeptidases and the free amino acids were absorbed. The aspartic acid moiety was transformed in large part to CO2 through its entry into the tricarboxylic acid cycle. Phenylalanine was primarily incorporated into body protein either unchanged or as its major metabolite, tyrosine.
Although aspartame was hydrolyzed in the gut of the monkey to its constituent moieties, methanol, aspartic acid, and phenylalanine, the ingestion of 15 or 60 mg/kg doses for 10 days did not modify phenylalanine metabolism. Aspartame had little effect on the disappearance of iv admin (14)C-phenylalanine from the plasma, it did not substantially affect the conversion of phenylalanine into tyrosine or carbon dioxide, and it did not alter the rate of incorporation of label into protein. The majority of phenylalanine derived from aspartame was incorporated into body protein, with only 20-25% of the compound being excreted. 60-80% of the derived methanol and aspartic acid was oxidized to carbon dioxide.
◉ Summary of Use during Lactation:Aspartame is not detectable in breastmilk after maternal ingestion because it is rapidly broken down in the mother's body. An extremely large intake of aspartame (equivalent to 17 cans of soda or 100 packets of Equal Sweetener) can slightly increase the amount of phenylalanine in breastmilk. Phenylalanine concentrations in milk return to baseline by 12 hours after a large single dose of aspartame. Although it is prudent to avoid the use of aspartame in women who are nursing an infant with phenylketonuria, amounts that are typically ingested in aspartame-sweetened foods and beverages do not result in any additional risk to breastfed infants with phenylketonuria. Ingestion of diet drinks containing low-calorie sweeteners might increase the risk of vomiting in breastfed infants.
◉ Effects in Breastfed Infants:A cross-sectional survey assessed the dietary history of US mothers nursing infants between 11 and 15 weeks of age. The survey was used to estimate the amount of diet soda and fruit drinks consumed by the women. There were no statistically significant differences in infants’ weight or z-scores based on low calorie sweetener exposure. However, infants exposed to low calorie sweetener in milk once or less per week had a statistically significantly higher risk of vomiting than those who were not exposed. Greater exposure was not associated with vomiting. It was not possible to assess the effects of specific sweeteners.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
... If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine ... , the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock...
Antimutagenic effects of combination of aspartame (0.4 and 4 mg/kg) and beta-carotene (0.15-15 mg/kg) were studied by estimation of chromosome aberrations in bone marrow cells of C57Bl/6 mice. Single and 5-day treatment with this combination decreased the clastogenic effects of dioxidine and cyclophosphamide and produced a more potent and universal antimutagenic effect than its constituents.
The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetener and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16 mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other molds. This mycotoxin contaminates animal feed and food. OTA is immunosuppressive, genotoxic, teratogenic, carcinogenic and is nephrotoxic in all animal species studied so far. OTA inhibits protein synthesis and induces lipid peroxidation. Since it seems impossible to avoid completely contamination of foodstuffs by toxigenic fungi, it is necessary to investigate the possible ways of limiting such toxicity. An attempt to prevent OTA-induced nephrotoxic and genotoxic effects, mainly the karyomegaly, has been made in vivo using aspartame (L-aspartyl-L-phenylalanine methyl ester), a structural analogue of both OTA and phenylalanine. Aspartame (25 mg/kg bw) prevented most of the nephrotoxic effects induced by OTA (289 ug/kg bw). It also showed some utility in preventing morphological and histological damage, mainly the karyomegaly.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
吸收
在小肠中被吸收，阿斯巴甜的代谢和吸收非常迅速。
Absorbed in the small intestine, aspartame is metabolized and absorbed very quickly.
[EN] IMIDAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS IMIDAZOLE UTILES COMME INHIBITEURS DE LA FAAH
申请人：MERCK & CO INC
公开号：WO2009152025A1
公开（公告）日：2009-12-17
The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.
[EN] PYRAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES COMME INHIBITEURS DE FAAH
申请人：MERCK & CO INC
公开号：WO2009151991A1
公开（公告）日：2009-12-17
The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease
[EN] COMPOUNDS FOR USE AS PROTON CHANNELS AND METHODS THEREOF<br/>[FR] COMPOSÉS DESTINÉS À ÊTRE UTILISÉS EN TANT QUE CANAUX DE PROTONS ET PROCÉDÉS ASSOCIÉS
申请人：AGENCY SCIENCE TECH & RES
公开号：WO2020159441A1
公开（公告）日：2020-08-06
The present disclosure relates generally to compounds or a salt, solvate, stereoisomer and prodrug thereof for forming synthetic membrane channels. The present disclosure also relates to methods of synthesizing the compounds, methods of forming the synthetic membrane channels and methods of use thereof. In particular, the synthetic membrane channels are synthetic proton channels in a lipid membrane.
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
[EN] OXAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS D'OXAZOLE UTILES COMME INHIBITEURS DE FAAH
申请人：MERCK & CO INC
公开号：WO2010017079A1
公开（公告）日：2010-02-11
The present invention is directed to certain oxazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.
