Amphetamine is known to be metabolized by the liver under the action of the CYP2D6. The metabolic pathway of amphetamine is mainly defined by aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation. The formed metabolites in this pathway are 4-hydroxyamphetamine, 4-hydroxynorephedrine, hippuric acid, benzoic acid, benzyl methyl ketone, and p-hydroxyamphetamine which is known to be a potent hallucinogen. However, a significant part of the original compound remains unchanged.
Amphetamine is metabolized in the liver by aromatic hyroxylation, N-dealkylation, and deamination. Although the enzymes involved in amphetamine metabolism have not been clearly defined, cytochrome P450 (CYP-450) 2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Because CYP2D6 is genetically polymorphic, population variations in amphetamine metabolism are a posibility.
Metabolism that results in aromatic hydroxylation, aliphatic hydroxylation, and n-dealkylation of amphetamines can give rise to active metabolites such as the potent hallucinogen p-hydroxyamphetamine. Other metabolic pathways, including deamination and subsequent side chain oxidation, produce inactive amphetamine derivatives.
来源:Hazardous Substances Data Bank (HSDB)
代谢
苯丙胺是 Fenproporex 的已知人体代谢物。
Amphetamine is a known human metabolite of Fenproporex.
IDENTIFICATION AND USE: Amphetamine is a colorless liquid with characteristic amine odor (similar to geranium leaves) and an acrid taste. It is used for the following indications: Psychostimulant: Accepted indications: Narcolepsy; Hyperkinetic states in children (as an adjunct to psychological, educational and social measures). The drug is misused for performance enhancement. Abuse either orally or by injection is extremely common. HUMAN EXPOSURE AND TOXICITY: Main risks include: acute central nervous system (CNS) stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Cardiovascular effects include: palpitation, chest pain, tachycardia, arrhythmias and hypertension; cardiovascular collapse can occur in severe poisoning, as well as, myocardial ischemia, infarction and ventricular dysfunction. CNS effects include: stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia. Stroke and cerebral vasculitis have been observed. Gastrointestinal effects include: vomiting, diarrhea and cramps. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary effects: increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Transient hyperthyroxinemia may be noted. Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Hypo- and hyperkalemia have been reported. Dehydration is common. Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Children appear to be more susceptible than adults and are less likely to have developed tolerance. The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. 65 children whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester, were studied. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. ANIMAL STUDIES: Testing for toxicity to the retina has been negative; 10 mg/kg given daily to dogs for three months caused occasional slight ophthalmoscopic appearance of blanching of the fundus, but no histologic change in the retina. The behavioral effects of d-amphetamine administration were studied in 17 adult cats. The doses of amphetamine administered were 0.1, 0.5, 1.0 and 5.0 mg/kg sc. Amphetamine administration induced a dose-dependent hypomotility, which was marked with the higher doses. In addition, rhythmic, bilateral slow movements of the head as a mode of stereotype, indifference to the environment and dose-dependent incr in respiratory rate were observed in amphetamine-treated cats. Amphetamine damages cerebral arteries in experimental animal models. ECOTOXICITY STUDIES: In the freshwater bivalve Dreissena polymorpha the bell-shaped trend of antioxidants showed at the highest tested amphetamine concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation.
Amphetamines stimulate the release of norepinephrine from central adrenergic receptors. At higher dosages, they cause release of dopamine from the mesocorticolimbic system and the nigrostriatal dopamine systems. Amphetamine may also act as a direct agonist on central 5-HT receptors and may inhibit monoamine oxidase (MAO). In the periphery, amphetamines are believed to cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors. Modulation of serotonergic pathways may contribute to the calming affect. The drug interacts with VMAT enzymes to enhance release of DA and 5-HT from vesicles. It may also directly cause the reversal of DAT and SERT.
Amphetamine is well absorbed in the gut and as it is a weak base hence the more basic the environment the more of the drug is found in a lipid-soluble form and the absorption through lipid-rich cell membranes is highly favored. The peak response of amphetamine occurs 1-3 hours after oral administration and approximately 15 minutes after injection and it presents a bioavailability of over 75%. Complete amphetamine absorption is usually done after 4-6 hours.
The elimination of amphetamine is mainly via the urine from which about 40% of the excreted dose is found as unchanged amphetamine. About 90% of the administered amphetamine is eliminated 3 days after oral administration. The rate of elimination of amphetamine highly depends on the urine pH in which acidic pH will produce a higher excretion of amphetamine and basic pH produces a lower excretion.
来源:DrugBank
吸收、分配和排泄
分布容积
苯丙胺报告称其具有高分布体积，为4 L/kg。
Amphetamine is reported to have a high volume of distribution of 4 L/kg.
The reported normal clearance rate is of 0.7 L.h/kg. This clearance has been shown to get significantly reduced in patients with renal impairment reaching a value of 0.4 L.h/kg.
来源:DrugBank
吸收、分配和排泄
儿童比成人更快地消除了安非他命。
Children: Children eliminated amphetamine faster than adults.
[EN] QUINUCLIDINE COMPOUNDS AS ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS<br/>[FR] COMPOSÉS QUINUCLIDINE EN TANT QUE LIGANDS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 DE L'ACÉTYLCHOLINE
申请人：BRISTOL MYERS SQUIBB CO
公开号：WO2016073407A1
公开（公告）日：2016-05-12
There are disclosed a series of quinuclidines having the Formula (I). which bind to the nicotinic α7 receptor and may be useful for the treatment of disorders of the central nervous system.
[EN] S-NITROSOMERCAPTO COMPOUNDS AND RELATED DERIVATIVES<br/>[FR] COMPOSÉS DE S-NITROSOMERCAPTO ET DÉRIVÉS APPARENTÉS
申请人：GALLEON PHARMACEUTICALS INC
公开号：WO2009151744A1
公开（公告）日：2009-12-17
The present invention is directed to mercapto-based and S- nitrosomercapto-based SNO compounds and their derivatives, and their use in treating a lack of normal breathing control, including the treatment of apnea and hypoventilation associated with sleep, obesity, certain medicines and other medical conditions.
The present invention relates to a series of novel compounds and derivatives thereof, methods to prevent or treat viral infections by using the novel compounds, processes for their preparation, their use to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, preferably infections with viruses belonging to the family of the Togaviridae and more preferably infections with chikungunya virus (CHIKV).
Tricyclic compounds, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.
三环化合物，其受保护的中间体，以及用于抑制HIV整合酶的方法被披露。
[EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
申请人：NOVO NORDISK AS
公开号：WO2005105736A1
公开（公告）日：2005-11-10
Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.
