Neuroleptic agents

The most prominent pharmacologic activity exhibited by phenothiazines bearing the 1,3-propyldiamine side chain is, of course, that of a neuroleptic agent. Treatment of psychoses and severe neuroses constitutes the largest single use of these so-called... 

A 36-year-old male unemployed dishwasher with no history of seizures presents with difficulty thinking coherently and claims that he is an astronaut. Following treatment, he suddenly has a grand mal seizure. Which neuroleptic agent was administered ... 

The answer is c. (Hardman7 p 408.) Clozapine differs from other neuroleptic agents in that it can induce seizures in nonepileptic patients In patients with a history of epileptic seizures for which they are not receiving treatment, stimulation of seizures can occur following the administration of neuroleptic agents because they lower seizure threshold and cause brain discharge patterns reminiscent of epileptic seizure disorders. 

To search for novel neuroleptic agents, attention has been given to structural modifications of dibenzoepines such as clozapine (9) [ 17] as a clinically active atypical antipsychotic, and its analogous fluperlapine (10) [18, 19] with a pharmacological resemblance to clozapine. Some 2-piperazinyl-5-phenyl-... 

Rimcazole (BW 234U) (496) is a novel anti-pyretic, neuroleptic agent. It was found to be a specific competitive antagonist of a-sites in the brain. It reverses psychotic conditions induced in humans by phencyclidine and/or a-opiod antagonists, probably by binding to receptors in the brain (459-461). Rimcazole has an indirect effect on dopamine neurons with relative selectivity for AlO dopamine cells (462). 

Some neuroleptic agents, like cycloindole (497), which has a modified tryptamine structure, and flucindole (498), a difluoro analog of cycloindole, have found use in therapy because of their anti-depressant and anti-psychotic activity (463,464) (Scheme 4.11). 3-Chlorocarbazole (385) (see Scheme 2.102), isolated from female bovine urine, has Diazepam-like activity (354). 

Table 6. Usual recommended doses and common side effects of neuroleptic agents used for psychosis or behavioral...

Fentanyl is 80 to 100 times as potent as morphine. Sufentanil (Sufenta) is 500- to 1,000-fold more potent than morphine, while alfentanil (Alfenta) is approximately 20 times more potent than morphine. Their onset of action is usually less than 20 minutes after administration. Dosage is determined by the lean body mass of the patient, since the drugs are lipophilic and tend to get trapped in body fat, which acts as a reservoir, prolonging their half-life. In addition, redistribution of the drugs from the brain to fat stores leads to a rapid offset of action. Droperidol, a neuroleptic agent, is generally administered in combination with fentanyl for IV anesthesia. 

Which neuroleptic agent has the lowest likelihood of producing tardive dyskinesia ... 

Jerling, M., Dahl, M.-L., °Aberg-Wistedt, A., Liljenberg, B., Lan-dell, N.-E., Bertilsson, L., and Sjoqvist, F. (1996) The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clin Pharmacol Ther 59 423-428. 

It is a short acting neuroleptic agent used in anaesthesia. 

All clinically effective antipsychotics block DA receptor activity. Further, stimulation of this neurotransmitter can induce psychotic symptoms de novo or exacerbate an existing psychotic disorder. Atypical agents have differential impacts on other systems (e.g., 5-HT) in comparison with the earlier neuroleptic agents. They also selectively target specific DA tracts that may mediate the pathological condition, while sparing those tracts that mediate the unwanted adverse effects (e.g., EPS, TD). 

Antibacterial Neuroleptic agent Antihypertensive Antilice/Antiscabies Nondepolarizing muscle-relaxing agent Antibiotic... 

Costall, B. Naylor, R. J. 1976, A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonise the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems, Eur.J.Pharmacol., vol. 40, no. 1, pp. 9-19. 

All of the following are observed in patients taking neuroleptic agents EXCEPT ... 

Q10 Haloperidol is an antipsychotic or neuroleptic agent. It is an antagonist at dopamine receptors, particularly of the D2 subtype. These drugs help to control the symptoms (mainly the positive symptoms) of schizophrenia by antagonizing the dopamine receptors in different brain areas, such as the frontal and temporal lobes. Antipsychotic agents, such as haloperidol, take days or weeks to achieve their therapeutic effect and may produce some motor disturbances. 

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

Other neuroleptic agents such as phenothiazines, which are non-selective dopamine antagonists, can cause endocrine dysfunction as well as extrapyra-midal side effects. 

Fines RE, Brady WJ Jr, Martin ML. Acute laryngeal dystonia related to neuroleptic agents. Am J Emerg Med 1999 17(3) 319-20. 

Knudsen P, Vilmar T. Cannabis and neuroleptic agents in schizophrenia. Acta Psychiatr Scand 1984 69(2) 162-74. 

Arrhythmias have been reported following the use of neuroleptic agents but are not specific to liver disease. However, there may be a greater risk in patients with hepatic impairment owing to accumulation of the drug. 

F., Sanchez-Abarca, E and Calleja, J., Synthesis of 3-aminomethyl-l-tctralones as potential neuroleptic agents. Ear. J. Med. Chem.,... 

SAFETY PROFILE Poison by ingestion and intravenous routes. Experimental teratogenic and reproductive effects. A neuroleptic agent. When heated to decomposition it emits very toxic fumes of Cr, F-, and NOx. 

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