benztropine and Substance-Related-Disorders

The design, synthesis and pharmacological evaluation of novel dopamine transporter ligands, based on Benztropine [3a-(diphenylmethoxy) tropane], has been a focus of our research efforts toward the development of novel cocaine-abuse pharmacotherapeutics. Structure-activity relationships at the dopamine transporter, for this series of compounds, have been derived and compared to those of cocaine and GBR 12909. These studies suggest that structurally diverse dopamine uptake inhibitors may access different binding domains on the dopamine transporter. The distinctive behavioral profile displayed in this series of compounds, as compared to cocaine and other dopamine uptake inhibitors, is of particular interest and is proposed to be relevant to the pharmacodynamic and pharmacokinetic properties of this class of tropane-based molecules.

Topics: Benztropine; Carrier Proteins; Cocaine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Drug Design; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Piperazines; Stereoisomerism; Structure-Activity Relationship; Substance-Related Disorders

The abuse and overdose of anti-cholinergic agents such as benztropine is well reported in the psychiatric and emergency medicine journals. However, despite almost 40 years since the first modern report, physicians in general remain poorly aware of anti-cholinergic abuse. A case report of recreational overdose of benztropine in a 19 year old schizophrenic patient is presented. Delirium and anti-cholinergic manifestations persisted for five days necessitating prolonged hospitalization. The literature on benztropine abuse and overdose is reviewed.

Topics: Adult; Benztropine; Drug Overdose; Humans; Male; Muscarinic Antagonists; Substance-Related Disorders

A 33-year-old man with a history of recreational benztropine abuse presented to the emergency department with confusion, abdominal pain, and distention. An abdominal radiograph revealed gross fecal loading. He was initially treated with intravenous fluids and opiate analgesia. Subsequently, a diagnosis of anticholinergic poisoning was made, based on tachycardia, delirium, dry mucosa, and reduced bowel sounds. Treatment with tacrine reversed the delirium, and a history of repeated benztropine use was obtained. Persistent ileus was treated with repeated doses of neostigmine, and gastrointestinal motility returned with prompt defecation. Neostigmine appears to be useful in reversing ileus caused by anticholinergic drug overdose. Theoretically, it may be useful in reversing anticholinergic ileus resulting from acute drug overdose, allowing or enhancing decontamination, but the safety and potential efficacy of neostigmine in this scenario have not been established.

Topics: Adult; Benztropine; Cholinergic Antagonists; Emergency Service, Hospital; Gastrointestinal Motility; Humans; Intestinal Obstruction; Male; Neostigmine; Substance-Related Disorders

The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission. Drugs that block dopamine (DA) uptake have generally been found to function as positive reinforcers. Benztropine (BZT) and several of its halogenated analogs have previously been characterized as potent DA-uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine.. The present experiments were designed to examine, in rhesus monkeys, the reinforcing effects of the DA-uptake inhibitor BZT and two chloro-analogs 3'-Cl-BZT and 4'-Cl-BZT, and to compare self-administration and binding profiles.. Four rhesus monkeys self-administered cocaine i.v. under a fixed-ratio 10 (FR10) schedule until stable responding was established. Saline, and various doses of cocaine, BZT, and the BZT analogs were then made available for self-administration. Binding of these compounds to monoaminergic and cholinergic sites in monkey brain were determined using standard radioligand binding techniques.. Self-administration was maintained by both 3'-Cl-BZT and 4'-Cl-BZT, but not by BZT. Results suggested that 3'-Cl-BZT and 4'-Cl-BZT were weak positive reinforcers. BZT and analogs bound DA transporters (DAT) with affinities higher than that of cocaine and had affinity for muscarinic binding sites.. Surprisingly, high affinity at DATs was associated with weak or no reinforcing effects. The mechanism(s) that may underlie this dissociation between DAT actions and reinforcing effects remains to be established. These data support the proposal that a lead for the discovery of a pharmacotherapeutic agent for cocaine abuse may come from this group of compounds.

Topics: Animals; Benztropine; Binding, Competitive; Brain; Conditioning, Operant; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Female; Injections, Intravenous; Macaca mulatta; Male; Radioligand Assay; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Self Administration; Substance-Related Disorders

This study assessed misuse of anticholinergic drugs in a population of 50 patients with serious mental illness who were assertively managed by a community-based outreach team in Sydney, Australia. One-third of the subjects reported having misused anticholinergics over the previous month. All anticholinergics were misused, and trihexyphenidyl (benzhexol) was misused most frequently. Most subjects misused at least one other drug as well. On direct questioning, the reason given most frequently was "to get high"; on indirect questioning, reasons were related more to peer participation and feelings of futility. Marginalized patients living in the community are vulnerable to the misuse of anticholinergic drugs.

Topics: Adult; Benztropine; Female; Humans; Illicit Drugs; Male; Mental Disorders; Muscarinic Antagonists; New South Wales; Orphenadrine; Prevalence; Procyclidine; Substance-Related Disorders; Trihexyphenidyl

Few investigations have assessed the neuropsychological effects of psychotropic medications on schizophrenic patients. In this study, 44 clinically stable schizophrenic inpatients were administered a battery of neuropsychological tests, and their performance was correlated with dosage of neuroleptic medication and benztropine. Neuroleptic dose was correlated with poorer performance on tests of psychomotor speed and attention, and with the number of perserverative errors on the Wisconsin Card Sort. Anticholinergic dose was associated with poorer verbal learning, verbal fluency, and motor speed. Both medication dosages were associated with poorer verbal recognition memory, but this association was strongly influenced by the performance of individuals on the highest medication doses. The findings, which were independent of clinical state and intelligence, indicate that higher doses of neuroleptic and anticholinergic medications are associated with poorer neuropsychological functioning in schizophrenia.

Topics: Adult; Antipsychotic Agents; Benztropine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders; Trihexyphenidyl

Topics: Adult; Benztropine; Catatonia; Humans; Male; Schizophrenia; Substance-Related Disorders

The addictive and euphorogenic effects of cocaine are thought to result primarily from inhibition of dopamine reuptake. Although the potency of cocaine-like drugs as inhibitors of DA reuptake is highly correlated with their potency as reinforcers in animals, several potent DA reuptake blockers (bupropion, nomifensine, benztropine, and mazindol) have not been reported to produce addiction or euphoria in humans. Based on these observations in humans, DA reuptake inhibitors are classified into two groups; type 1 blockers, which produce addiction and euphoria, and type 2 blockers, which do not. Given that type 1 and type 2 blockers act at the same site (the DA transporter), the author suggests that type 2 agents may antagonize the effects of cocaine, and might prove useful in the treatment of cocaine addiction.

Topics: Benztropine; Bupropion; Cocaine; Dopamine; Drug Evaluation, Preclinical; Humans; Mazindol; Nomifensine; Propiophenones; Substance-Related Disorders

Topics: Adult; Affect; Benztropine; Female; Humans; Male; Middle Aged; Parasympatholytics; Schizophrenia; Substance-Related Disorders; Trihexyphenidyl

A 27-year-old neuroleptic-stabilised schizophrenic patient presented with a three-day history of psychomotor retardation, disturbed sleep, and social and emotional withdrawal following reduction of his anticholinergic dosage; his symptoms had intensified after an increase in neuroleptic dosage, based on a diagnosis of psychotic decompensation. Recognition of a cholinergic syndrome and institution of appropriate anticholinergic treatment resulted in rapid improvement. The clinical distinction between a cholinergic overdrive state and schizophrenic exacerbation, while sometimes difficult, can be critical in selecting appropriate management.

Topics: Adult; Benztropine; Brain; Humans; Imipramine; Male; Marijuana Abuse; Receptors, Cholinergic; Schizophrenia, Paranoid; Substance Withdrawal Syndrome; Substance-Related Disorders; Syndrome; Thiothixene; Tropanes

Topics: Adult; Benztropine; Diphenhydramine; Humans; Male; Schizophrenic Psychology; Smoking; Substance-Related Disorders; Tropanes

1. This report describes two cases of psychotic syndrome from benztropine (Cogentin), which was used to treat haloperidol-induced extrapyramidal side effects. The patients' symptomatology meets DSM III criteria for delirium. Both patients displayed repetitive motor automatisms (stereotypy). 2. Symptomatology appeared one-to-two days after the start of benztropine 2 mg b.i.d. and subsided one-to-several days after benztropine was stopped. Treatment consisted of administration of sedative hypnotic drugs. 3. The literature on anticholinergic-induced psychotic syndromes is surveyed. Particular attention is drawn to the occurrence of stereotypy. 4. It is proposed, on the basis of a review of animal and clinical data, that stereotypies in delirious patients are related to muscarinic blockade in the central nervous system. This model is used to explain repetitive motor automatisms which are seen in Alzheimer's disease. 5. The paper concludes with brief guidelines for the management of anticholinergic delirium.

Topics: Adult; Aged; Benztropine; Delirium; Diazepam; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Ethchlorvynol; Female; Haloperidol; Humans; Imipramine; Phenobarbital; Psychoses, Substance-Induced; Stereotyped Behavior; Substance-Related Disorders; Tropanes

Abuse of the antiparkinsonian agents for their hallucinogenic and euphoriant effects is likely more prevalent than reported. Two clinical cases are presented, with discussion of symptoms and response to a diagnostic trial of physostigmine.

Topics: Adult; Antiparkinson Agents; Benztropine; Female; Humans; Male; Physostigmine; Psychoses, Substance-Induced; Substance-Related Disorders; Trihexyphenidyl

A review of the literature indicates that the anticholinergic antiparkinson drugs can be abused by some patients to achieve pleasurable effects ranging from a mild euphoria with increased sociability at the lower doses to a toxic anticholinergic psychosis with disorientation and hallucinations at higher doses. Trihexyphenidyl may have a greater potential for abuse but there has been no systematic data on this issue. While the abuse of these drugs may not be widespread, it is yet another factor arguing for their judicious use.

Topics: Antiparkinson Agents; Benztropine; Euphoria; Humans; Substance-Related Disorders; Trihexyphenidyl

Thirty-two cases of drug-induced dystonic reaction were treated by the author with diphenhydramine or benztropine mesylate, intramuscularly or intravenously, in a prospective, nonrandomized fashion. Recovery time with the two drugs was compared. Benztropine mesylate lessened recovery time in this case series. An epidemiological study of drug-induced dystonic reactions found that most of the patients were drug abusers. The commonest offensive agent in this case series was haloperidol. The most common dystonic reactions seen were buccolingual and torticollic.

Topics: Adolescent; Adult; Benztropine; Diphenhydramine; Dystonia; Female; Haloperidol; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Substance-Related Disorders

Topics: Amphetamines; Barbiturates; Benzodiazepines; Benztropine; Cocaine; Drug and Narcotic Control; Forecasting; Hallucinogens; Humans; Morphinans; Morphine Derivatives; Nonprescription Drugs; Phencyclidine; Substance-Related Disorders; United States