Information on the metabolism of BZ in humans is limited, but Benzylic Acid (BA) and 3-Quinuclidinol are the probable main metabolites ... . It has been estimated that 3% of the BZ is excreted as the parent compound.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Male mice administered neostigmine in the drinking water a daily increasing concentrations (20-100 mg/L) for four days became tolerant to its toxicity and presented a reduced binding of [3H]quinuclidinyl benzilate ([3H]QNB) in the small intestine. An increased binding of [3H]QNB was found in the forebrains of neostigmine-treated animals. This was due to an increase in muscarinic cholinergic receptor density. ... Administration of methylatropine together with neostigmine prevented the decrease of [3H]QNB binding in the small intestine as well as the increase in the forebrain.
Emergency Department Care: Once decontamination has occurred, the primary emphasis simply is supportive care of exposed patients. Emergency department staff must be certain that proper decontamination has occurred. Dermal absorption and off gassing of QNB does occur and can pose a risk to hospital personnel. In patients who are not protecting their airway, perform intubation and mechanical ventilation. Apply soft restraints to patients at risk of harming themselves or health care workers. Intravenous hydration may be necessary; maintain adequate urinary output. If urinary retention is suggested, place a Foley catheter. For patients experiencing marked agitation, consider benzodiazepine administration. In patients with hyperthermia, cooling measures may be necessary. Completely remove the patient's clothing. Insert a Foley catheter or rectal temperature probe. Administer adequate intravenous fluids. Cooling measures such as evaporative cooling using skin wetting with directed circulating fans, ice water immersion, ice packs, and cooling blankets may be necessary. Include continuous cardiac and core temperature monitoring.
Physical examination is the key to diagnosing the causative agent /in a terrorist event/. After exposure to QNB, the physical examination is consistent with an anticholinergic syndrome. ... Depending on the dose and time postexposure, a number of CNS effects may manifest. Restlessness, apprehension, abnormal speech, confusion, agitation, tremor, picking movements, ataxia, stupor, and coma are described. Hallucinations are prominent, and they may be benign, entertaining, or terrifying to the patient experiencing them. ... Simple tasks typically performed well by the exposed person may become difficult. ... Mydriasis resulting in photophobia is expected. Impairment of near vision occurs because of loss of accommodation and reduced depth of field secondary to ciliary muscle paralysis and pupillary enlargement. If QNB is splashed into the eye, conjunctival injection and eye pain also occur. Tachycardia is a prominent feature of QNB exposure. Heart rates may be rapid but rarely exceed 150 beats per minute. Exacerbated heart rate responses to exertion also are expected. Systolic and diastolic blood pressure may show moderate elevation. A decrease in capillary tone may cause skin flushing. Gastrointestinal: Intestinal motility slows, and secretions from the stomach, pancreas, and gallbladder decrease. Nausea and vomiting may occur. Decreased or absent bowel sounds are noted on examination. Respiratory: ... dry mucus membranes of the mouth and throat are noted. Speech may decrease to a whisper. Breath of the exposed patient may develop a foul odor. Skin: Inhibition of sweating results in dry skin. Place hands directly into the axilla of the exposed patient and note the absence of moisture. Red flushed skin also may occur. Urinary: Urination is difficult or impossible. Subsequent urinary retention may occur, and an enlarged bladder may be palpable on examination.
Physical: Of final note on the examination is an increase in deep tendon reflexes. Anticholinergic effects on the Renshaw interneurons in the spinal cord cause hyperreflexia.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
QNB通常以气溶胶形式传播，主要通过呼吸系统吸收。也可以通过皮肤或胃肠道吸收。
QNB usually is disseminated as an aerosol, and the primary route of absorption is through the respiratory system. Absorption also can occur through the skin or gastrointestinal tract.
Bioavailability via ingestion and by inhalation of one-micron particles approximates 80%, and 40 to 50%, respectively, of a parenterally delivered dose of BZ. Percutaneous absorption of BZ dissolved in propylene glycol yields, after a latent period of up to 24 hours, serum levels approximately 5 to 10% of those achieved with intravenous or intramuscular administration. ... Following absorption, BZ is systemically distributed to most organs and tissues of the body. Its ability to reach synapses and neuromuscular and neuroglandular junctions throughout the body is responsible for its peripheral nervous system (PNS) effects, whereas its ability to cross the blood-brain barrier confers upon it the ability to cause CNS effects. Atropine and hyoscyamine both cross the placenta and can be found in small quantities in breast milk; whether this is also true for BZ is unclear.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
大多数进入体内的QNB通过肾脏排出，因此尿液是检测的首选。
Most of the QNB that enters the body is excreted by the kidneys, making urine the choice for detection.
5-Membered heterocyclic allylsilanes in synthesis: Generation via aza-ene reaction and application to the synthesis of a bicyclic 1,2-dinitrogen analogue of naturally occurring pyrrolizidines
摘要：
A cyclic hydrazide containing an allylsilane functionality obtainable by an aza-ene reaction provides ready access to a bicyclic 1, 2-dinitrogen compound related to naturally occurring pyrrolizidines. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
Provided is a novel therapeutic agent for chronic obstructive pulmonary disease.
Provided are a quinuclidine derivative and a medicament comprising the quinuclidine derivative.
wherein R
1
represents a hydrogen atom, a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group; Y represents —C(C═O)—O—, —CH
2
—, or —CH
2
O—; m represents an integer of 1 to 5; Z represents an oxygen atom or a sulfur atom; l represents a number of 0 or 1; n represents an integer of 0 to 4; X
−
represents an anion; and a substituent of a quinuclidine ring represents a 1,3-bond, or 1,4-bond, provided that when m is 3, l is 1, and n is 0, R
1
represents a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group.
human muscarinic M3 receptor (hM3R), has both anti-inflammatory and short-acting bronchodilatory activities. To obtain MP derivatives with longer-lasting bronchodilatory activity, we synthesized hybrid compounds based on MP and two other muscarinic antagonists with long-acting bronchodilatory activity glycopyrronium bromide (GC) and aclidinium bromide (AD). Of these three synthesized hybrid compounds
Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof
申请人：——
公开号：US20030105071A1
公开（公告）日：2003-06-05
One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various mammalian cellular receptors, including G-protein coupled receptors. A third aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors or transporters. Another aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors. The compounds of the present invention will also find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, Tourette's syndrome, psychiatric disorders, stroke, senile dementia, peptic ulcers, pulmonary obstruction disorders, and asthma.
Chemical or isotopic labels are added to, e.g., a potentially lethal drug formulation, to generate a unique chemical fingerprint. Combinations of chemical additives are mixed with the drug to aid in their isolation and identification, especially when such drugs are used for illicit purposes. When stable isotopes are incorporated into lethal drugs, the labeling process conveys a very unique internal chemical signature and greatly aids in the identification of the parent drug in body fluids and tissues. When heath-care providers become aware that certain drugs can now be easily tracked and identified in a victim, individuals may be reluctant to utilize these agents for ill purposes.
