The phenethylamine-derived designer drug 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) was found to be mainly metabolized in rats by O-demethylation, N-acetylation, hydroxylation of the ethyl side chain at C2' or at C1' followed by oxidation at C1' to the corresponding ketone, by deamination followed by reduction to the corresponding alcohols or by oxidation to the corresponding acids, and finally combinations of these steps. Most of the metabolites were excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC-MS allowed the detection of an intake of a dose of 2C-E in rat urine that corresponds to a common drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-E in human urine. /4-Ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E)/
The in vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), a ring-substituted psychoactive phenethylamine, was studied in rat. Male Wistar rats were administered 10 mg/kg 2C-T-7 hydrochloride orally, and 24-hr urine fractions were collected. After enzymatic hydrolysis of the urine sample, the metabolites were extracted by liquid-liquid extraction and analyzed by liquid chromatography/mass spectrometry. 2C-T-7-sulfoxide, N-acetyl-2C-T-7-sulfoxide, N-acetyl-2,5-dimethoxy-4-methylthiophenethylamine-sulfoxide, N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfoxide, and N-acetyl-2,5-dimethoxy-4-(2-hydroxypropylthio)phenethylamine-sulfone were detected as the primary metabolites of 2C-T-7. These findings suggest that sulfoxidation, sulfone formation, hydroxylation of the propyl side chain at the beta-position, and S-depropylation followed by methylation of thiol were the major metabolic pathways of 2C-T-7 in rat.
Studies are described on the metabolism and the toxicological analysis of the phenethylamine-derived designer drug 2,5-dimethoxy-4-ethylthio-beta-phenethylamine (2C-T-2) in rat urine using gas chromatography/mass spectrometry (GC/MS) after enzymatic cleavage of conjugates, liquid-liquid extraction and derivatization. The structures of 14 metabolites were assigned tentatively by detailed interpretation of their mass spectra. Identification of these metabolites indicated that 2C-T-2 was metabolized by sulfoxidation followed by N-acetylation and either hydroxylation of the S-ethyl side chain or demethylation of one methoxy group, O-demethylation of the parent compound followed by N-acetylation and sulfoxidation, deamination followed by reduction to the corresponding alcohol followed by partial glucuronidation and/or sulfation or by oxidation to the corresponding acid followed either by partial glucuronidation or by degradation to the corresponding benzoic acid derivative followed by partial glucuronidation. Furthermore, 2C-T-2 was metabolized by N-acetylation of the parent compound followed either by O-demethylation and sulfoxidation or by S-dealkylation, S-methylation and sulfoxidation. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction microwave-assisted acetylation allowed the detection of an intake of a dose of 2C-T-2 in rat urine, which corresponds to a common drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-T-2 in human urine. /2,5-Dimethoxy-4-ethylthio-beta-phenethylamine (2C-T-2)/
Basic Treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Encourage patient to take deep breaths. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Irritating materials/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Early intubation at the first sign of upper airway obstruction may be necessary. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... Use proparacaine hydrochloride to assist eye irrigation ... . /Irritating materials/
/SIGNS AND SYMPTOMS/ 2C-T-7 produces negative physical and psychological effects in users. Physical effects include visual and auditory disturbances and distortions, increased blood pressure, blurred vision, dehydration, dilated pupils, headaches, irregular heartbeat, jaw clenching, nausea, and vomiting. Psychological effects associated with the use of 2C-T-7 include emotional distress, hallucinations, inability to sleep, irritability, loss of memory, nervousness, restlessness, and tension. Additionally, 2C-T-7 can cause impaired judgment, leading abusers to engage in dangerous activities. Compounding these risks is the uncertainty of the 2C-T-7 dosage in a particular tablet, capsule, or quantity of powder--high dosages can cause overdoses and death. At least three deaths have been associated with 2C-T-7 abuse.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
人类毒性摘录
/症状和体征/ 2C-T-7滥用与人类癫痫发作有关。
/SIGNS AND SYMPTOMS/ 2C-T-7 abuse has been associated with convulsions in humans.
... the primary route of administration is oral. However, insufflation (snorting) is also commonly mentioned in user reports. Some less common routes of administration include smoking, rectal administration and intravenous or intramuscular administration.
[EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DU RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
申请人：ARENA PHARM INC
公开号：WO2015066344A1
公开（公告）日：2015-05-07
Provided are 5-HT2C receptor agonists. Also provided are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent.
[EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DES RÉCEPTEURS 5-HT2C, COMPOSITIONS ET MÉTHODES D'UTILISATION
申请人：ARENA PHARM INC
公开号：WO2018035477A1
公开（公告）日：2018-02-22
The present invention relates to compounds of Formula A and pharmaceutical compositions thereof that modulate the activity of the 5-HT2C receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of a 5-HT2C receptor-mediated disorder, such as, weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction and the like, obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders, urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a compound herein, optionally in combination with a supplemental agent.
Synthesis of deuterium labeled phenethylamine derivatives
作者：Ya-Zhu Xu、Chinpiao Chen
DOI：10.1002/jlcr.1139
日期：2006.11
The synthesis of a series of five deuteriumlabeledphenethylaminederivatives, 4-bromo-2,5-[2H6]-dimethoxyphenethylamine (2C-B), 4-chloro-2,5-[2H6]-dimethoxyphenethylamine (2C-C), 2,5-[2H6]-dimethoxy-4-iodophenethylamine (2C-I), 2,5-[2H6]-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-[2H6]-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) from 1,4-[2H6]-dimethoxybenzene is described. The isotopically
[EN] COMPOSITIONS COMPRISING TRYPSIN-CLEAVABLE AMPHETAMINE PRODRUGS AND INHIBITORS THEREOF<br/>[FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS DE TYPE AMPHÉTAMINE CLIVABLES PAR TRYPSINE ET LEURS INHIBITEURS
申请人：PHARMACOFORE INC
公开号：WO2011133347A1
公开（公告）日：2011-10-27
Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an amphetamine prodrug that provides enzymatically-controlled release of amphetamine or an amphetamine analog. The composition can further comprise an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of amphetamine or the amphetamine analog from the amphetamine prodrug so as to attenuate enzymatic cleavage of the amphetamine prodrug.
COMPOSITIONS FOR REDUCING RISK OF ADVERSE EVENTS CAUSED BY DRUG-DRUG INTERACTIONS
申请人：JENKINS Thomas E.
公开号：US20120232066A1
公开（公告）日：2012-09-13
The present disclosure provides a composition comprising a GABA
A
agonist and a GI enzyme inhibitor. The present disclosure also provides a composition comprising (a) a GI enzyme inhibitor and (b) a first drug that interacts with a second drug to produce an adverse effect when the second drug is co-ingested as a GI enzyme-cleavable prodrug with the first drug. Such an interaction can be additive or synergistic.
