Antipsychotic drugs neuroleptics

Typical antipsychotic drugs Neuroleptic dtugs conventional antipsychotic diugs older antipsychotic diugs ... 

Butyrophenones A family of typical antipsychotic drugs (neuroleptics), the most commonly used being haloperidol. 

A principal interest in our laboratory is the molecular characterization of CNS receptor sites of the neurotransmitter dopamine (DA, 5). These sites are strongly implicated in the biochemical etiology of schizophrenia and Parkinson s Disease, as well as other diseases of the CNS (50,51). Thus, the rank order of clinical potency of antipsychotic drugs (neuroleptics) correlates with the affinity of these drugs for dopaminergic sites (52,53), It is also well established that Parkinson s disease is directly related to deterioration in dopaminergic neurotransmission in the corpus striatum, which is a brain region rich in dopamine receptor sites (54). The use of L-DOPA, the biosynthetic precursor of dopamine, in treatment of patients with Parkinson s disease is one of the best examples of biochemically directed medical treatment. 

All drugs listed in Part IV Antipsychotic Drugs (Neuroleptics) can cause extrapyrami-dal symptoms (EPS) and tardive dyskinesia (TD), although Clozaril and Phenergan are weaker dopamine blockers with less of a tendency to cause these adverse effects. 

The antipsychotic drugs (neuroleptics) are effective in controlling many manifestations of psychotic illness. Though the disease is not cured by drug therapy, the symptoms of sehizophrenia, ineluding thought disorder, emotional withdrawal, and hallucinations or delusions, may be attenuated by antipsychotic drugs. Unfortunately, protracted therapy (years) is often needed and ean result in severe toxicity in some patients. 

Dopamine Receptors - All antipsychotic drugs (neuroleptics) are known to block DA receptors. The number of receptor subtypes claimed for DA, based on binding studies, include "D-1, D-2, D-3 and D-4". 5 However, only the postsynaptic D-2 receptors (labeled by 3[H]butyrophenones) are most consistently relatable to the effects of drugs. The D-1 subtype, a DA-stimulated adenylate cyclase site, has no clearcut function in brain. 46 Recent studies on agonist binding disclosed that 3[h]DA binds to two sites, both postsynaptic one is related to D-2 sites and the other to D-1 sites. 47... 

Antipsychotic, or neuroleptic drug Used in the treatment of schizophrenia. They are also used in the management of psychotic episodes associated with psychotropic drug toxicity and some neurodegenerative disorders. 

FIGURE 58-7 The IC50 values (ordinate) are the concentrations of the antipsychotic drugs that reduce the stereospecific component of 3H-haloperidol binding by 50%. The abscissa indicates the average values (and ranges) of doses used for schizophrenia. (From Seeman, P. et al. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261 717-719,1976)... 

McShane R, Keene J, Gedling K et al. (1997) Do neuroleptic drugs hasten cognitive decline in dementia Prospective study with necropsy follow up. BMJ 314(7076) 266-270 Mortimer AM, Shepherd CJ, Rymer M et al. (2005) Primary care use of antipsychotic drugs an audit and intervention study. Ann Gen Psychiatry 4 18 DOI 10.1186/1744-859X-4-18 Mulsant BH, Pollock BG, Kirshner M et al. (2003) Serum anticholinergic activity in a community-based sample of older adults relationship with cognitive performance. Arch Gen Psychiatry 60(2) 198-203... 

Clozapine and olanzapine are atypical antipsychotic drugs used in the treatment of schizophrenia. Their strnctnres are depicted in Scheme 2.36. The use of clozapine and olanzapine, which are more effective than standard neuroleptic drugs in the treatment of refractory schizophrenia, is, however, limited becanse of their adverse effects. These adverse effects are ascribed to the formation of the corresponding cation-radicals in living organisms under oxidation by bone marrow cells. These cation-radicals eliminate protons from the NH fragments and generate their nitrenium cations. The nitreninm cations are covalently bonnd to the life-important proteins. This results in the toxic effects of clozapine and olanzapine (Sikora et al. 2007). 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

It also seems plausible that antipsychotic drugs competitively bind with dopamine receptors and block the action of dopamine on corresponding receptor sites, thus lowering psychotic activity. Central dopamine receptors are subdivided into Dj, D2, and according to some sources, Dj receptors. These receptors have a high affinity for dopamine, but they differ in sensitivity to neuroleptics of various chemical classes. For example, drugs of the phenothiazine series are nonselective competitive Dj and D2 antagonists. Unlike phenoth-iazines, antipsychotics of the butyrophenone series such as haloperidol display selective action only on D2 receptors. 

Trifluoperazine is one of the most active antipsychotic drugs. A moderate stimulatory effect accompanies the neuroleptic effect. Trifluoperazine is unique in that, patients instead of the usual stiffness and weakness characteristic of phenothazine derivatives, become more lively. This drug has a strong anticonvulsant activity. It is widely used in psychiatry for treating schizophrenia and other mental illnesses. The most common synonyms are mobadid, triftazin, stelazine, cahnazin, and others. 

Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with promethazine alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (eg, irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias). 

Neuroleptic malignant syndrome (NMS) NMS is a potentially fatal condition reported in association with antipsychotic drugs and with amoxapine. 

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