Ephedrine is largely unmetabolized in the body. Ephedrine can be N-demethylated to norephedrine, or demethylated and deaminized to benzoic acid conjugates and 1,2-hydroxypropylbenzene.
... After /volunteers (n=3 for each drug) consumed a single clinical dose of ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) or cathine/..., urine samples were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6 hr and disappeared in urine at approximately 24-48 hr post-administration. For MEPH, the peaks of excretion extended from 4 to 12 hr post-administration and were undetectable at approximately 48 hr. A single clinical dose of EPH (25 mg) may exceed threshold level (10 ug/mL) in sport drug testing if the urine samples are tested within approximately 8 hr post-administration. However, a single dose of MEPH (20 mg) never reached the threshold value (10 ug/mL).
The metabolism of ephedrine in humans, dogs and several species of rodents proceeds primarily by three reactions; aromatic hydroxylation, N-demethylation, and oxidative deamination. The extent to which ephedrine is metabolized and the major metabolites vary quantitatively between species. The extent of aromatic hydroxylation is greatest in rats, followed by rabbits, guinea pigs, and dogs, with no aromatic hydroxylation observed in humans. N-demethylation of ephedrine is greatest in rabbits followed by dogs, guinea pigs, rats, and humans. Deamination is greatest in rabbits, followed by humans and rats. Ephedrine, 8-20%, is metabolized in humans by N-demethylation to /phenylpropanolamin/ PPA. A total of 4-13% of an oral dose of ephedrine undergoes oxidative deamination yielding 1-phenylpropan-1,2-diol and further side-chain oxidation to benzoic acid and hippuric acid.
来源:Hazardous Substances Data Bank (HSDB)
代谢
产量L-去甲麻黄碱和兔苯甘醇。/来自表格/
Yields L-norephedrine and phenylglycol in rabbits. /from table/
来源:Hazardous Substances Data Bank (HSDB)
代谢
消除途径：主要经肾
半衰期：3-6小时
Route of Elimination: mainly renal
Half Life: 3-6 hours
IDENTIFICATION: Ephedrine is a colorless or white solid powder or crystals. It has a bitter taste and is odorless or slight aromatic odor. It is soluble in water, alcohol, chloroform, ether, glycerol, olive oil and in liquid paraffin. Ephedrine and its optical isomer pseudoephedrine are structurally very similar to methamphetamine. In illicit drug laboratories simple dehydrogenation is used to make methamphetamine from ephedrine. Indications: The most important uses are: as a bronchodilator; nasal decongestant; and treatment for syndrome of Stokes-Adams; as a mydriatic and hypertensor in the spinal anesthesia. It is also used as an herbal diet supplement under the name Ma-huang as an anorectic and CNS stimulant. HUMAN EXPOSURE: Contraindications: Cardiovascular disease; hypertension; hyperthyroidism; pheochromocytoma and closed angle glaucoma. Ephedrine should not be given in patients being treated with MAOI (or have stopped treatment in the last 14 days). It should be used with caution in patients with prostatic enlargement or with renal impairment. Routes of exposure: Oral: Abuse of ephedrine-containing diet pills is a common occurrence. Inhalation: Ephedrine salts are used as nasal drops or sprays in the relief of nasal congestion associated with cold or rhinitis. Ephedrine can be abused by the nasal route by subjects who have developed dependence to its vasoconstrictive effect. Dermal: As an ointment is well absorbed. Eye: Eye-drops at 0.1% are effective in congestion of conjunctival allergy. Parenteral: Subcutaneous or intramuscular injections. Kinetics: Absorption by route of exposure: Ephedrine is readily and completely absorbed from the gastrointestinal tract; plasma peak concentrations are reached an hour after ingestion. Biological half-life by route of exposure: It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH. No change in half-life from that seen with therapeutic dosing was observed in an otherwise healthy patient with massive overdose. Metabolism: Only a small amount of ephedrine is metabolized in the liver. Elimination by route of exposure: It is largely excreted unchanged in the urine, with some deaminated metabolites and N-demethylated metabolites. Elimination is enhanced in acid urine. Mode of action: Toxicodynamics: Ephedrine can produce stimulation at the adrenergic receptors and neuronal norepinephrine release. Pharmacodynamics: Ephedrine has both alpha- and beta-adrenergic activities, and both direct and indirect effects on receptors. It raises blood pressure both by increasing cardiac output and inducing peripheral vasoconstriction. It can produce bronchodilation. In local application it causes pupils dilation. The main metabolic effects in overdose are hyperglycemia and hypokalemia. Ephedrine is a centrally acting respiratory stimulant and can increase motor activity. Interactions: A serotonin syndrome has been reported in a patient taking paroxetine and an over the counter cold medicine containing ephedrine. Combination of ephedrine and a monoamine oxidase inhibitor can produce life-threatening reactions. It should also be avoided in patients undergoing anesthesia with cyclopropane, halothane or other volatile anesthesia. An increased risk of arrhythmias may occur if given to patients receiving cardiac glycosides, quinidine or tricyclic antidepressants, ergot alkaloids and oxytocin. Main adverse effects: Central effects of sympathomimetic agents include: tremor, fear, anxiety, confusion, irritability, insomnia, and psychotic states. Paranoid psychosis, delusions and hallucinations may also follow ephedrine overdose. Effects on the cardiovascular system are complex: vasoconstriction, hypertension, or hypotension and bradycardia, tachycardia, palpitations, cardiac arrest. It can cause local ischemia in chronic topical use. Clinical effects Acute poisoning: Ingestion: Early clinical manifestations of ingestion of high doses of ephedrine consist of nausea and vomiting, followed by insomnia, cardiac arrhythmia, myocardial ischemia, agitation, psychosis and seizures. Parenteral exposure: The parenteral use of ephedrine may cause intracerebral hemorrhage as a result of a rise in arterial pressure. Ventricular arrhythmias have been described. Ingestion: Neurological symptoms that have been described include headache, anxiety, tremor, insomnia, dizziness, seizures. Several cases of psychosis have been reported. Cardiovascular disorders associated with the chronic use of ephedrine may include chest pain, hypertension, arrhythmia, myocardial infarction, cerebral vasculitis and stroke. Skin exposure: Local applications of ephedrine may cause contact dermatitis. Parenteral exposure: The intravenous use of ephedrine causes similar effects as oral ingestion. Other: The vasoconstrictive effects of ephedrine applied topically as nasal spray or drops may cause local ischemia. Course, prognosis, cause of death: Early clinical manifestations of ephedrine overdose consist of nausea and vomiting, followed by headache, agitation, anxiety, tremor, seizures, tachycardia and hypertensive crisis. Severe rise in blood pressure may produce cerebral hemorrhage and myocardial infarction. Ventricular arrhythmia may progress to cardiac arrest and death. Although fatalities have been reported the prognosis is usually good. Systematic description of clinical effects: Cardiovascular: The most common symptoms are arterial hypertension and tachycardia; ventricular arrhythmia, chest pain, myocardial infarction, ischemic or hemorrhagic stroke, cardiac arrest may rarely occur. Respiratory: Respiratory stimulation, bronchodilation, pulmonary edema and apnea. Neurological: CNS: CNS stimulation: anxiety, agitation, tremor, mental confusion, hallucinations, mania, paranoid psychosis may occur; convulsions have been reported. Autonomic nervous system: Ephedrine causes stimulation of the sympathetic nervous system acting on both alpha and beta receptors. Symptoms include tachycardia, arterial hypertension, tremor, sweating, mydriasis. Skeletal and smooth muscle: Ephedrine produces relaxation of smooth muscle. In overdose it may also cause rhabdomyolysis. Gastrointestinal: Nausea and vomiting are common. Urinary: Ephedrine relaxes the vesical detrusor muscle, and increases contraction of the vesical sphincter (alpha agonist action), and can produce acute retention of urine. Dermatological: Eye, ear, nose, throat: local effects: Chronic administration of nasal drops or spray can result in rebound nasal congestion and rhinorrhea. Hematological: Leukopenia. Metabolic: Acid base disturbances and metabolic acidosis or has been observed. Fluid and electrolyte disturbances: Hypokalemia resulting from intracellular shift. Allergic reactions: Contact dermatitis after local application. Sensitization and systemic allergic reactions (severe eczema) have been reported after oral administration. Other clinical effects: Special risks: Ephedrine is present in breast-milk in sufficient concentrations to be harmful to the baby, and is contraindicated in women who are breast-feeding. Patients with ischemic heart disease, hypertension, acute angle glaucoma, hyperthyroidism, prostatic enlargement, or taking monoamine oxidase inhibitor antidepressants should also avoid ephedrine. Other: Chronic use can lead to tolerance with dependence. Ephedrine abuse is a common occurrence and has been associated with several deaths.
Ephedrine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
Ephedrine is mainly eliminated in the urine. Approximately 60% is eliminated as the unmetabolized parent compound, 13% as benzoic acid conjugates, and 1% as 1,2-dihydroxypropylbenzene.
来源:DrugBank
吸收、分配和排泄
分布容积
口服麻黄碱的平均分布体积为215.6升。
Oral ephedrine has an average volume of distribution of 215.6L.
来源:DrugBank
吸收、分配和排泄
清除
口服麻黄碱的清除率为23.3升/小时，但患者间的变异性很大。
Oral ephedrine has a clearance of 23.3L/h but there is a high degree of inter-patient variability.
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。
3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
申请人：Xue Chu-Biao
公开号：US20060004018A1
公开（公告）日：2006-01-05
The present invention is directed to compounds of Formula I:
which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.
The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.
本发明涉及环丙胺衍生物，这些衍生物是LSD1抑制剂，可用于治疗癌症等疾病。
CYCLIC ETHER PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
申请人：Genentech, Inc.
公开号：US20140088117A1
公开（公告）日：2014-03-27
Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein R
2
is a cyclic ether and X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
