Loxapine 45

Ultimately, it became clear that the antipsychotic action, EPS liabilities, and serum prolactin elevations of this class of antipsychotics resulted from the antagonism of the DA D2 receptors in the limbic system, dorsal striatum, and anterior pituitary gland, respectively. The positive correlation between in vitro DA receptor occupancy and average clinical dose suggested that for typical antipsychotic drugs such as haloperidol and chlorpromazine, antipsychotic activity, EPS liabilities, and prolactin elevations were closely linked to DA receptor blockade.53'54 Positron emission tomography (PET) studies demonstrated that therapeutic response to most antipsychotic drugs occurs when >65-70% of striatal D2 receptors were blocked, even though this was mainly a measure of the region of the brain where EPSs are mediated. Because EPSs were shown to occur more commonly at a D2 receptor occupancy of >80%, a 'therapeutic window' of 60-80% D2 receptor blockade has been proposed as a means of striking a balance between the need for enough D2 receptor blockade to achieve clinical efficacy and the importance of avoiding EPS. None of these measures is particularly relevant to clozapine or quetiapine, two atypical antipsychotic drugs, which are effective as antipsychotic drugs at much lower occupancy of striatal D2 receptors than is the case for typical neuroleptic drugs, olanzapine, risperidone, and ziprasidone.

Because of their side effects and lack of efficacy against multiple symptom domains, and the development of more effective and tolerable agents, the above drugs no longer represent the preferred treatment for schizophrenia. Results from a recent NIMH-sponsored clinical trial (Clinical Antipsychotic Trials of Intervention Effectiveness; CATIE), however, have suggested that the use of first-generation antipsychotics be revisited. This study, which has only been partially reported,55 suggested that perphenazine 31, a first-generation drug, may be comparable in efficacy to quetiapine 46, risperidone 47, and ziprasidone 48, and only moderately less effective than olanzapine 49, which had more metabolic side effects than the other drugs. There are, however, numerous limitations with this study with regard to dosage, patient population inclusion criteria, prior antipsychotic medications, and primary endpoint, which preclude definitive conclusions regarding the preferred treatment for schizophrenia. Additionally, it has been noted that the CATIE is one of some 25 trials comparing antipsychotic agents. While the first generation of antipsychotic drugs is much cheaper than the newer drugs, at least at the present time, they cannot be recommended over the newer agents on the basis of cost effectiveness, spectrum of efficacy, or overall side effects. In particular, the risk of tardive dyskinesia is so much greater with first-generation antipsychotic drugs that they should not be substituted for the atypical antipsychotic drugs without clear warning to patients of the risk they are incurring by so doing.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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