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At least 55 records · Page 3Linked to original sources
PubMed1994

Multiunit activity from the A9 and A10 areas in rats following chronic treatment with different neuroleptic drugs.

Effects of repeated twice daily i.p. administration of haloperidol (0.5 mg/kg), clozapine (3.0 mg/kg) and prothipendyl (1.0 mg/kg) on spontaneous A9 and A10 cell activity were studied using extracellular multiunit recording in rats, which offers relatively rapid access to neural activity in a large number of cells. Two cell types were identified, which probably represent the putative dopaminergic and non-dopaminergic neurons. Repeated neuroleptic treatment reduced the number of spontaneously active type 1 A10 cells per track. The effect of haloperidol was more pronounced than that of clozapine or prothipendyl. A9 cells were affected by haloperidol only. The frequency and amplitude of A9 and A10 active cells remained quite stable, except for a clozapine-induced increase of their values for type 1 A10 cells. Stability of spontaneously active type 1 A10 cells was significantly reduced by the chronic neuroleptic treatment. Collectively the activity of type 2 cells was not altered. Prothipendyl was classified as an atypical neuroleptic drug with potency comparable to clozapine.

Animals↗
PubMed2002

Fatal accident caused by isoflurane abuse.

A fatal accident after isoflurane abuse is presented in this report. A hospital employee was found dead in the operating area with a plastic bag over his head. In his locker an almost empty bottle of isoflurane was found. Autopsy revealed signs of asphyxiation and toxicological examination revealed nordazepam and isoflurane in non-toxic concentrations in the blood. Quantification of the anaesthetic was also carried out in urine, gastric contents, liver, kidney and brain samples, and in addition, oxazepam, prothipendyl and metabolites of midazolam and prothipendyl were found in the urine. Although the drug problems of the deceased were known before, no efforts had been made to restrict access to these drugs.

Accidents↗
PubMed2001

Different fatal toxicity of neuroleptics identified by autopsy.

Autopsies and toxicological analyses at the Institute of Forensic Medicine revealed 85 fatal intoxications with neuroleptics in Vienna from 1991 to 1997. A total of 17 cases were linked to a single neuroleptic (NL) alone, while 68 deaths were attributed to a combination of NLs with other drugs. The most frequently detected agent was prothipendyl (n=41). During the study period the number of defined daily doses of high-potency NLs prescribed increased significantly (P< or =0.001) due to increased prescribing of new atypical antipsychotics. The quantity of intermediate- and low-potency NLs dispensed remained stable. The most frequently prescribed NL was haloperidol. The relative toxicities of different NLs were calculated by dividing the number of deaths caused by this NL into the number of defined daily doses prescribed in the observation period (f-value). Single-substance intoxications and multiple-substance intoxications were distinguished. The highest f-values were associated with low-potency NLs, especially with prothipendyl, chlorprothixene and levomepromazine. Low f-values were found for the group of high-potency NLs, including flupentixol, fluphenazine, haloperidol and pimozide, as well as olanzapine. Compared to the f-values for all NLs prescribed, f-values for low-potency NLs were shown to be significantly higher concerning single-substance intoxications (P< or = 0.05) and multiple-substance intoxications (P < or = 0.001), while f-values for high-potency NLs were significantly lower (P< or = 0.05 and P< or = 0.001). We are not aware of the psychiatric diagnoses in our post-mortem sample. However, the present results indicate that careless use of low-potent NLs should be avoided in patients with a potential risk of accidental or suicidal overdose.

Adult↗
PubMed1997

Phototoxic properties of neuroleptic drugs.

BACKGROUND: Photo-induced eruptions are well-known adverse effects of some neuroleptic drugs, particularly chlorpromazine. OBJECTIVE: By a photohemolysis test we assessed in vitro the phototoxic properties of 12 phenothiazines (chlorpromazine, dixyrazine, fluphenazine, levomepromazine, perazine, perphenazine, promazine, promethazine, prothipendyl, thioridazine, trifluoperazine, triflupromazine) and 5 thioxanthenes (chlorprothixene, clopenthixol, flupenthixol, thiothixene, zuclopenthixol). METHODS: Human erythrocytes from 3 donors were incubated with the compounds and irradiated with light sources rich in UVA or UVB, respectively. Doses were up to 100 J/cm2 UVA or up to 1,600 mJ/cm2 UVB. Photo-induced hemolysis was calculated as percentage of complete hemolysis. RESULTS: Photo-induced hemolysis >10% due to radiation rich in UVA was found with chlorpromazine (maximal median: 98%), dixyrazine (100%), fluphenazine (84%), perazine (100%), perphenazine (100%), promazine (16%), promethazine (25%), prothipendyl (96%), trifluoperazine (100%), triflupromazine (76%), chlorprothixene (100%) and thiothixene (31%). UVB-rich radiation induced hemolysis only with chlorpromazine (73%), dixyrazine (45%) and perazine (60%). CONCLUSION: Most neuroleptics are strongly phototoxic in vitro indicating a potential risk for photo-induced reactions also to occur in patients treated with these drugs.

Antipsychotic Agents↗
PubMed1992

Different neuroleptics show common dose and time dependent effects in quantitative field potential analysis in freely moving rats.

Under the assumption that field potentials recorded from particular brain areas reflect the net balance of neurotransmitter activities, the dose- and time-dependent responses induced by intraperitoneal application of different neuroleptic drugs are quantified by spectral analysis of the electroencephalogram recorded from frontal cortex, hippocampus, striatum and reticular formation. The actions of haloperidol, chlorpromazine, clozapine, prothipendyl and thioridazine in general were characterized by increases of the spectral power in the alpha 1 and beta range, at higher dosages also in the theta range. This observed pattern of changes is in line with the neuroleptic induced spectral changes reported in the literature for other animals and man. In the light of the already known effects of other psychoactive drugs on the frequency content of field potentials in the rat, it should now be possible to classify different drugs in terms of their clinical indication. With respect to the type of neurotransmitter control underlying the changes produced by various neuroleptics, it is quite obvious from the comparisons with the respective drug effects that dopamine-D1-receptor controlled transmission is not responsible for this action. On the basis of earlier findings a possible interaction between dopamine-D2 receptor or glutamatergic transmitter control is discussed.

Animals↗
PubMed1996

Combined intoxication with a tricyclic antidepressive agent and a neuroleptic.

We report the case of a patient who co-ingested a tricyclic antidepressant (2500 mg of doxepin) and a neuroleptic drug (3500 mg of prothipendyl). Following overdose either agent can affect the central nervous and cardiovascular systems, inducing arrhythmias, conduction disturbances and hypotension. The presented case illustrates that a combined overdose of tricyclic antidepressants and neuroleptics enhances the possible toxic effects of each drug and especially the risk for adverse cardiac events. The clinical features and management of this combined intoxication are discussed. Treatment with sodium bicarbonate readily corrected a potentially life-threatening cardiac arrhythmia and is therefore suggested to be imperative in the treatment of these cases.

Adult↗
PubMed2000

Successful prolonged cardiopulmonary resuscitation after a combined intoxication with a tricyclic antidepressant, a benzodiazepine and a neuroleptic.

We report the case of a patient who co-ingested a tricyclic antidepressant (amitriptyline), benzodiazepines (alprazolam and lormetazepam) and a neuroleptic drug (prothipendyl). Major neurologic and cardiac symptoms occurred including a prolonged cardiac arrest. The cardiopulmonary resuscitation phase was complicated by a haematoma of the liver treated by a left hepatectomy. The clinical features and management of this combined intoxication are discussed.

Adult↗
PubMed1994

The role of serotonin receptor subtypes in the behavioural effects of neuroleptic drugs. A paw test study in rats.

The present study was designed to evaluate the roles of serotonin 5-HT1A and 5-HT2 receptors in the effects of neuroleptic drugs in the paw test. This behavioural test has been shown to model both the antipsychotic efficacy as well as the extrapyramidal side-effect liability of neuroleptic drugs. Whereas the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) reduced the effects of the classical neuroleptic haloperidol, it increased the effects of the atypical neuroleptic clozapine. The 5-HT2 receptor antagonist ketanserin as well as the 5-HT1C/5-HT2 receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) reduced the effects of clozapine. The most important finding, however, was that the behavioural effects of different (putative) neuroleptics (fluphenazine, SCH-39166, remoxipride, prothipendyl, thioridazine and risperidone) were differentially influenced by both 8-OHDPAT and DOI, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subclasses of classical and atypical neuroleptics.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Medication-induced headache: overview and systematic review of therapeutic approaches.

OBJECTIVE: To review medication-induced headache (MIH) through a systematic evaluation of the literature regarding the pharmacologic management of this condition. METHODOLOGY: To identify and evaluate all pharmacologic interventions for MIH, we conducted a qualitative systematic review of the English-language literature from 1966 to June 1998 using MEDLINE. The following search terms were used: chronic daily headache, transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache, medication-induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from relevant literature was also conducted to collect reports not identified in the MEDLINE search. RESULTS: Numerous therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone, piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long-term prognosis of therapy are discussed and therapeutic guidelines are offered. CONCLUSIONS: MIH is an underrecognized and difficult condition affecting headache-prone patients. The published literature concerning treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate therapy. Recognition and treatment of MIH may lead to a long-term improvement in headache relief for many patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term results.

Amitriptyline↗
PubMed1975

Antiaccelerator and decelerator activity of eleven phenothiazine derivatives.

Eleven N-substituted phenothiazine derivatives were studied for their antiaccelerator and decelerator activities on the dog heart. The antiaccelerator activity was determined in heart-lung preparation in dogs. Taking into consideration the percentage inhibition of cardio-acceleration produced by continuous infusion of 3 mug/min of adrenaline, all the drugs except chlorpromazine and 10-butyl-phenothiazine in two experiments caused more than 50 percent inhibition. 10-Propylphenothiazine induced maximum inhibitory effect, i.e. 90.1 percent in a total dose of 20 mg. Two types of effects were observed upon impulse generation in the sinus node. Acceleration was produced by chlorpromazine, 10-cyclopentyl-phenothiazine, prothipendyl, and thiazinamium, which was very short-lived, whereas other drugs produced deceleration. The correlation between antiaccelerator and decelerator properties is rather a close one.

Animals↗
PubMed1992

[Neuroleptic malignant syndrome--a case report].

The occurrence of a malignant neuroleptic syndromes accompanied by urinary retention under the treatment with fluphenazine and prothipendyl in a mentally disabled psychotic is reported. Early recognition of the syndrome and immediate termination of the neuroleptic treatment lead to its spontaneous remission. Subsequent neuroleptic treatment by clozapine was tolerated without further complications.

Adult↗
PubMed1980

Electrocardiographic changes in rats during chronic treatment with antidepressant and neuroleptic drugs.

Five antidepressants, 3 phenothiazines and 5 butyrophenone neuroleptics were administered to rats orally at maximally tolerated doses for 22 weeks. The electrocardiogram (ECG) was recorded weekly. In animals treated with antidepressants quinidine-like changes of the atrioventricular and intraventricular conduction developed. There were also elevation of T-wave and right rotation of the electrical axis. Dibenzepine had the least effect on the ECG. In the group of phenothiazines chlorpromazine induced tachycardia and thioridazine widening of the QRS complex. Prothipendyl had no effect. ECG-changes induced by some of the butyrophenone derivatives were tachycardia and widening of the QRS-complex. In rats treated with protriptyline the ECG changes were correlated with drug concentrations in serum and myocardial tissue. The studies provided a quantitative assessment of the cardiac effects of clinically proven psychotropic drugs. They will be useful as a baseline for the preclinical evaluation of new derivatives.

Animals↗