Antipsychotic drugs mechanism of action

Typical (first-generation) antipsychotic drugs - mechanism of action... 

The answer is c. (Hardman, pp 574—575.) Phencyclidine is a hallucinogenic compound with no opioid activity Its mechanism of action is amphetamine-like. A withdrawal syndrome has not been described for this drug in human subjects. In overdose, the treatment of choice for the psychotic activity is the antipsychotic drug haloperidol. 

Strange, P. G. Antipsychotic drugs importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol. Rev. 53 119-133, 2001. 

Miyamoto S, Dnncan GE, Marx CE, et al. Treatments of schizophrenia a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 2005 10 79-104. 

TCAs in more serious forms of depression such as melancholic or psychotic depression. Some studies have suggested that the SSRls do not work as well as the TCAs in melancholic depression (Roose et al. 1994]. Likewise, one study has suggested that venlafaxine, a drug with a mechanism of action similar to that of the TCAs, was superior to fluoxetine in the treatment of inpatients with melancholic depression (Clerc et al. 1994]. Still, other metaanalyses have failed to find a difference in the efficacy of SSRls versus TCAs in serious forms of depression [Nierenberg 1994]. Nonetheless, given that most studies have employed TCAs, and some debate exists about the utility of SSRls in severe subtypes, it may be prudent to start with a TCA in most patients until the debate is further resolved. For patients who present a significant suicide risk or who have not been able to tolerate TCAs, the SSRls in combination with a standard antipsychotic appears an effective option. 

D2 receptor, albeit with different specificity. Older examples of dopamine antagonists are chlorpromazine, haloperidol and many derivatives of these prototype compounds. Newer antipsychotic drugs such as risperidone, olanzapine and quetiapine have retained this mechanism of action, although no longer exclusively. 

Reserpine, used as a folk medicine in India, was found to have antipsychotic properties at about the same time as CPZ. Both agents affected the dopaminergic system, albeit in different ways, but the functional results were similar (i.e., lowering dopamine activity). This phenomenon has continued to be an important factor in hypotheses about the mechanism of action of these drugs and for biological theories about the pathophysiology of psychotic disorders. 

One common denominator of all antipsychotics is the biockade of centrai dopamine (DA) receptors. As a result, extrapyramidal reactions, particularly parkinsonian symptoms, are a major adverse effect of many of these drugs, as well as an important clue to their mechanism of action. True Parkinson s disease is caused by a DA deficiency in the nigrostriatal system. Further, crystallographic data have demonstrated that CPZ s molecular configuration is similar to that of DA, which could explain its ability to block this neurotransmitter s receptors. Drugs with similar structures that do not block DA receptors (e.g., promethazine, imipramine) do not have antipsychotic activity. Another example is the isomer of flupenthixol, which blocks DA receptors is an effective antipsychotic, but the isomer that does not is ineffective (7). The other family of dopamine receptors, D and Dg, have not yet been implicated in psychosis. 

The earliest effective treatments for schizophrenia and other psychotic illnesses arose from serendipitous clinical observations rather than from scientific knowledge of the neurobiological basis of psychosis or the mechanism of action of effective antipsychotic agents. Thus, the fist antipsychotic drugs were discovered by accident in the 1950s when a putative antihistamine (chlorpromazine) was serendipitously observed to have antipsychotic effects when tested in schizophrenic patients. Chlorpromazine indeed has antihistaminic activity, but its therapeutic actions in schizophrenia are not mediated by this property. Once chlorpromazine was observed to be an effective antipsychotic agent, it was tested experimentally to uncover its mechanism of antipsychotic action. 

Be able to understand the unique psychopharmacological mechanisms of action of the major antidepressants, anxiolytics, antipsychotics, cognitive enhancing agents, and drugs of abuse. 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

Dean B, Scarr E. Antipsychotic drags evolving mechanisms of action with improved therapeutic benefits. Curr Drug Targets CNS Neurol Disord. 2004 3 217-225. 

Kinan, B. J. and Lieberman, J. A. Mechanism of action of atypical and antipsychotic drugs - a critical analysis. Psychopharmacol. 124 (1996) 2-12. 

It is not clear that so-called antipsychotic drugs are superior to other types of drugs with sedative effects but different mechanisms of action. Lithium, benzodiazepines and opium have been shown to be comparable to neuroleptics in the treatment of psychotic states in some studies. The ability of the neuroleptic drugs to reduce the most characteristic symptoms of psychosis such as hallucinations, delusions and thought disorder have often been interpreted as evidence of their specifically antipsychotic or antischizophrenic action (The National Institute of Mental Health Psychopharmacology Service Center Collaborative Study... 

The discovery of the atypical antipsychotic clozapine opened a new era and set new standards in the drug treatment of schizophrenia. Modifications of the diben-zoazepine structure in clozapine resulted in olanzapine and quetiapine, which are among the most frequently used antipsychotic drugs. From a chemical viewpoint, clozapine, olanzapine and quetiapine can be considered as structural analogues. Although they share some common features in their molecular mechanism of action, the three compounds show significant differences in their clinical efficacy and adverse event profile. 

Laruelle M, Frankie WG, Narendran R, Kegeles LS, Abi-Dargham A. 2005. Mechanisms of action of antipsychotic drugs From dopamine D2 receptor antagonism to glutamate NMDA facilitation. Clin Ther 27(suppl. A) S16-S24. 

Abi-Dargham A, Laruelle M. 2005. Mechanisms of action of second generation antipsychotic drugs in schizophrenia Insights from brain imaging studies. Eur Psychiatry 20 15-27. 

A new, so-called third generation of antipsychotics has recently been introduced, and at this time one drug, aripiprazole, is available and others are in the late stages of development. This new class of medications has a novel mechanism of action that, at least in theory, should deal with several of the limitations of other atypicals. It will be remembered that all antipsychotics preceding this class had the ability to block the dopamine receptor, and they did so in all four dopamine pathways. As discussed, this had both benefits and drawbacks dopamine blockade resulted in the improvement of positive symptoms (mesolimbic pathway) but had a limited benefit in negative symptom reduction (mesocortical... 

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