piperidines and Poisoning

A MEDLINE search from 1966-1996 revealed no reports of cisapride poisoning. An 8-mo-old, 8.9 kg girl received 8 mL of cisapride (Propulsid Suspension, 1 mg/mL, Janssen Pharmaceutica, Titusville, NJ) rather than the usual dose of 0.8 mL, resulting in an inadvertent, 10-fold, iatrogenic, dosing error. She developed emesis, hyperactive bowel sounds, abnormal behavior, mild hyperthermia, tachycardia, hypertension, and thrombocytosis. This is the first published report of poisoning with cisapride.

Topics: Administration, Oral; Cisapride; Drug Labeling; Drug Overdose; Female; Humans; Infant; Parasympathomimetics; Piperidines; Poisoning

To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths.. The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected.. In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied.. Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

Topics: Autopsy; Humans; Piperidines; Poisoning; Retrospective Studies; Suicide

陈某，男，27岁，因工作、感情、生活等压力厌世。某日陈某独自骑摩托车旅行，于3月15日入住某民宿，并先后于实体药店和网上平台购买药物。3月22日民宿到期，房东联系不上陈某，敲门不应，遂报警。民警上门查探时发现房门为反锁状态，强行破门后发现陈某已死亡。为明确死亡原因，对其进行法医学鉴定。.

Topics: Chlorides; Ethanol; Humans; Piperidines; Poisoning; Potassium Chloride

Topics: Age Factors; Benzofurans; Child, Preschool; Female; Humans; Indoles; Infant; Isoxazoles; Male; Piperazines; Piperidines; Poisoning; Psychotropic Drugs; Risk Factors; Time Factors; Vilazodone Hydrochloride

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework.

Topics: Adult; Anesthetics, Dissociative; Fatal Outcome; Humans; Male; Piperidines; Poisoning

Diphenidine (1-(1,2-diphenylethyl)piperidine) and its 2-methoxylated derivative methoxphenidine (MXP, 2-MeO-diphenidine) are substances with dissociative effects that were recently introduced for "recreational" purpose through the online-based sale of new psychoactive substances (NPS). A number of analytically confirmed non-fatal intoxications associated with diphenidine or MXP have occurred in Sweden and were included in the STRIDA project.. Observational case series of consecutive patients with admitted or suspected intake of NPS and requiring intensive treatment in an emergency room and hospitalization in Sweden.. Blood and urine samples were collected from intoxicated patients presenting at emergency departments all over the country. NPS analysis was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during telephone consultations with the Poisons Information Centre and retrieved from medical records. Information was also obtained from online drug discussion forums.. Over a 12-month period from January to December 2014, 750 cases of suspected NPS intoxication originating from emergency departments were enrolled in the STRIDA project of which 14 (1.9%) tested positive for diphenidine and 3 (0.4%) tested positive for MXP. Co-exposure to several other NPS (e.g., 5-/6-(2-aminopropyl)benzofuran, 2-4-bromomethcathinone, butylone, 3,4-dichloromethylphenidate, 5-methoxy-N-isopropyltryptamine, methiopropamine, and α-pyrrolidinopentiothiophenone), also including other dissociative substances (3-/4-methoxyphencyclidine), and classical drugs of abuse (e.g., cannabis and ethanol) was documented in 87% of these cases. The 17 patients were aged 20-48 (median: 32) years, and 13 (76%) were men. They commonly presented with hypertension (76%), tachycardia (47%), anxiety (65%), and altered mental status (65%) including confusion, disorientation, dissociation, and/or hallucinations. Eight patients (47%) displayed severe intoxication (Poisoning Severity Score 3). The diphenidine- or MXP-positive patients required hospitalization for 1-3 (median: 2) days. In addition to standard supportive therapy, half of the cases were treated with benzodiazepines and/or propofol.. The adverse effects noted in analytically confirmed cases of NPS intoxication involving diphenidine or MXP were similar to those reported for other dissociative substances such as ketamine and methoxetamine. However, the high proportion of polysubstance use might have played a role in the intoxication and clinical features in some cases.

Topics: Adult; Chromatography, Liquid; Drug Overdose; Emergency Medical Services; Female; Hospital Costs; Hospitalization; Humans; Illicit Drugs; Male; Mass Spectrometry; Middle Aged; Piperidines; Poison Control Centers; Poisoning; Predictive Value of Tests; Psychotropic Drugs; Severity of Illness Index; Substance Abuse Detection; Sweden; Time Factors; Treatment Outcome; Young Adult

Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

Topics: Acetylcholinesterase; Alkaloids; Animals; Antidotes; Chemical Warfare Agents; Donepezil; Dose-Response Relationship, Drug; Galantamine; Guinea Pigs; Indans; Lethal Dose 50; Male; Phenylcarbamates; Piperidines; Poisoning; Rivastigmine; Sesquiterpenes; Soman; Time Factors; Toxicity Tests, Acute

We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.

Topics: Adolescent; Blood Glucose; Carbamates; Diagnosis, Differential; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Mental Disorders; Piperidines; Poisoning

Classical emergency treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). In subjects taking pyridostigmine and trained to autoadminister at least one autoinjector at the first signs of poisoning, classical emergency treatment ensures survival but only an antiglutamatergic compound like gacyclidine appears to be able to ensure optimal management of nerve agent poisoning in terms of rapid normalization of EEG activity, clinical recovery and total neuroprotection. All of this reinforces the therapeutical value of gacyclidine, which is in the process of approval for human use in France for treatment of head injury, as a central nervous system protective agent for the treatment of OP poisoning.

Topics: Atropine; Cholinesterase Reactivators; Cyclohexanes; Cyclohexenes; Electroencephalography; Excitatory Amino Acid Antagonists; Humans; Organophosphate Poisoning; Piperidines; Poisoning; Pyridostigmine Bromide; Self Administration

Organophosphorus (OP) nerve agents are still used as warfare and terrorism compounds. Classical delayed treatment of victims of organophosphate poisoning includes combined i.v. administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). The objective of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an antiglutamatergic compound, as a complement to the above therapy against organophosphate poisoning. Gacyclidine was injected (i.v.) in combination with atropine/diazepam/pralidoxime at man-equivalent doses after a 45- or 30-min latency period to intoxicated primates (2 LD50). The effects of gacyclidine on the animals' survival, electroencephalographic (EEG) activity, signs of toxicity, recovery after challenge and central nervous system histology were examined. The present data demonstrated that atropine/diazepam/pralidoxime alone or combined with gacyclidine did not prevent signs of soman toxicity when treatment was delayed 45 min after poisoning. Atropine/diazepam/pralidoxime also did not control seizures or prevent neuropathology in primates exhibiting severe signs of poisoning when treatment was commenced 30 min after intoxication. However, in this latter case, EEG recordings revealed that additional treatment with gacyclidine was able to stop soman-induced seizures and restore normal EEG activity. This drug also totally prevented the neuropathology observed 5 weeks after soman exposure in animals treated with atropine/diazepam/pralidoxime alone. Overall, in the case of severe OP-poisoning, gacyclidine represents a promising adjuvant therapy to the currently available polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in a human clinical trial for a different neuroprotective indication. However, it should always be kept in mind that, in the case of severe OP-poisoning, medical intervention must be conducted as early as possible.

Topics: Animals; Anticonvulsants; Antidotes; Atropine; Brain; Cerebellum; Cerebral Cortex; Chemical Warfare Agents; Cholinesterase Reactivators; Cyclohexanes; Cyclohexenes; Diazepam; Drug Therapy, Combination; Electrocardiography; Excitatory Amino Acid Antagonists; Haplorhini; Macaca fascicularis; Male; Piperidines; Poisoning; Pralidoxime Compounds; Seizures; Soman; Time Factors

Diphenidol (Cephadol, Vontrol), an antiemetic agent used in the treatment of vomiting and vertigo, has been reported to cause various adverse effects including drowsiness, hypotension, confusion, hallucination, restlessness, and other antimuscarinic effects. Serious toxic effects might be anticipated after intentional or accidental ingestion.. Retrospective analysis of all case records of the PCC-Taiwan defining diphenidol overdose during 1985-1996.. The data of 21 patients with diphenidol overdose were analyzed; 17 were < 3 years old and unintentionally poisoned, in contrast to the suicide attempts by four adults. The average amount of ingestion was 222.5 mg with a range of 25-800 mg. Most patients manifested only transient CNS, cardiovascular, or oculo-facial effects, but four children suffered from severe toxicity after an ingestion of 11.7-80 mg/kg diphenidol. Commonly reported toxicity in diphenidol overdose included facial flush (10), tachycardia, restlessness (6), seizures (4), dyspnea, drowsiness, mydriasis, coma, and fever (3). With supportive therapy, a good recovery was the rule except for one fatality of a 2 1/2-year-old boy who ingested 15 mg/kg diphenidol and presented with recurrent seizures, hypotension, respiratory failure, and coma.. Although not previously reported, accidental diphenidol overdose may result in serious anticholinergic toxicity in children. Treatment is supportive and the therapeutic role of physostigmine in diphenidol poisoning is still unclear.

Topics: Adult; Aged; Antiemetics; Child, Preschool; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Infant; Male; Middle Aged; Piperidines; Poison Control Centers; Poisoning; Retrospective Studies; Severity of Illness Index; Treatment Outcome

This study consists of two parts, first to compare the pharmacological profile of atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various rat brain structures, binding properties were determined by competition experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively. Competition curves have shown that atropine presents similar nanomolar inhibition constants toward each subtype, while CEB-1957 has distinct affinities (Ki from 0.26 to 73 nM) with the following range order: M3 > or = M2 > M1. The second part is to compare atropine and CEB-1957 (in combination with pralidoxime) for their ability to protect against the lethality induced by 2 x LD50 of the acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10 times lower than atropine. Finally, from these results, it is proposed that a selective blockade of M2 and M3 receptor subtypes could play a pivotal role in the protective effect against sarin poisoning.

Topics: Animals; Atropine; Autoradiography; Binding, Competitive; Brain; Cholinesterase Inhibitors; Male; Muscarinic Antagonists; Parasympatholytics; Piperidines; Pirenzepine; Poisoning; Rats; Rats, Wistar; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic; Sarin; Thiophenes

A case of lorcainide poisoning with fatal outcome is reported. A young girl of 15 ingested, without high lethality of intent, 2500 mg lorcainide, an antiarrhythmic agent. Bradycardia, shock, coma, and cerebral convulsions rapidly occurred. Despite immediate resuscitative measures with high doses of catecholamines and hypertonic sodium bicarbonate the patient died three hours later. The course of lorcainide poisoning was similar to that of other class Ic antiarrhythmic agents.

Topics: Adolescent; Anti-Arrhythmia Agents; Benzeneacetamides; Fatal Outcome; Female; Humans; Piperidines; Poisoning; Suicide

In experiments on male rats, the effect of selected cholinolytic agents (atropine, benactyzine, G 3063) in combination with the reactivator of cholinesterases HI-6 on the cholinergic and non-cholinergic effects of GV substance in the course of acute sublethal intoxication was compared. The cholinergic affects of GV substance were examined by means of the changes in the activity of cholinesterases in whole blood, the CNS, diaphragm and liver, the noncholinergic stressogenic effects by means of the changes in the level of corticosterone in plasma and the activity of tyrosine amino transferase in the liver. It follows from the changes in the activity of cholinesterases that the cholinergic effects of GV substance are least influenced by atropine, whereas benactyzine and G 3063 exert an approximately similar effect. The difference in the effect is evident especially in the 24th hour of intoxication. Similarly stressogenic effects of GV substance are least influenced by an antidotal combination of atropine and HI-6. It means that the centrally acting cholinolytic agents benactyzine and G 3063 are more advantageous for the therapy of GV substance poisonings than the peripherally acting atropine.

Topics: Acute Disease; Animals; Atropine; Benactyzine; Cholinergic Antagonists; Cholinesterase Reactivators; Cholinesterases; Male; Organophosphorus Compounds; Oximes; Piperidines; Poisoning; Pyridinium Compounds; Rats; Rats, Wistar; Tyrosine Transaminase

Risperidone is an investigational antipsychotic agent currently being tested in an international multicenter drug trial. We report the first case of a risperidone overdose in an apparent suicide attempt. This was without serious clinical side effects and manifested mainly as ECG abnormalities.

Topics: Adult; Antipsychotic Agents; Electrocardiography; Humans; Isoxazoles; Male; Piperidines; Poisoning; Risperidone; Suicide, Attempted

The protective effect of three dithiocarbamates against lung tissue damage induced by a single intratracheal instillation of cadmium chloride was examined in rats. The relative efficacy of these compounds was tested by comparing characteristic features of lung tissue damage: the increase of lung weight, and the changes in the synthesis and content of structural proteins. Of three compounds administered intraperitoneally at a dose of 2.46 mmol/kg body weight, the most effective in suppressing lung damage was sodium bis(hydroxyethyl)dithiocarbamate (DEDTC). Its efficacy was dependent on the time interval between administration of cadmium chloride and the DEDTC. The parameters of lung tissue damage which were examined approached control values when DEDTC and cadmium chloride were administered simultaneously.

Topics: Animals; Cadmium; Cadmium Poisoning; Connective Tissue; Copper; Ditiocarb; Lung; Lung Diseases; Male; Organ Size; Piperidines; Poisoning; Rats; Rats, Inbred Strains; Sorbitol; Thiocarbamates; Zinc

Topics: Child, Preschool; Diazepam; Drug Therapy, Combination; Female; Furosemide; Gastric Lavage; Histamine H1 Antagonists; Humans; Piperidines; Poisoning; Thiophenes

Topics: Animals; Diphenylacetic Acids; Female; Ganglionic Blockers; Male; Parasympatholytics; Piperidines; Poisoning; Rats; Sulfates

Topics: Alkylation; Animals; Antidotes; Creatinine; Ergolines; Ethylamines; Histamine; Histamine H1 Antagonists; Malates; Male; Methysergide; Mice; Mustard Compounds; Piperidines; Poisoning; Pyrazoles; Pyrrolidines; Serotonin; Serotonin Antagonists

Topics: Alcoholic Intoxication; Barbiturates; Bromides; Humans; Methaqualone; Paraldehyde; Piperidines; Poisoning; Renal Dialysis

Topics: Alcoholic Intoxication; Aluminum; Aminopyrine; Anti-Inflammatory Agents; Ascorbic Acid; Benzyl Compounds; Child; Child, Preschool; Cosmetics; Female; Hallucinations; Humans; Hyperkinesis; Male; Methylamines; Nalidixic Acid; Perfume; Phenethylamines; Piperidines; Poisoning; Pyrazoles; Rutin; Shock; Speech Disorders

Topics: Child; Child, Preschool; Dichlorodiphenyldichloroethane; Diuresis; Electroencephalography; Exchange Transfusion, Whole Blood; Female; Humans; Infant; Infusions, Parenteral; Male; Neurologic Manifestations; Oxazines; Peritoneal Dialysis; Piperidines; Poisoning; Pyrimidines; Renal Dialysis

Topics: Nursing; Piperidines; Poisoning

Topics: Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Glutethimide; Humans; Piperidines; Poisoning; Suicide

Topics: Glutethimide; Humans; Piperidines; Poisoning

Topics: Anticonvulsants; Glutethimide; Heparin; Piperidines; Poisoning

Topics: Barbiturates; Bemegride; Piperidines; Poisoning

Topics: Anticonvulsants; Glutethimide; Humans; Piperidines; Poisoning

Topics: Barbiturates; Piperidines; Poisoning; Thiazoles

Topics: Barbiturates; Bemegride; Piperidines; Poisoning

Topics: Barbiturates; Central Nervous System Stimulants; Piperidines; Poisoning; Thiazoles

Topics: Ascomycota; Barbiturates; Coma; Piperidines; Poisoning; Thiazoles