In 2010 antipsychotic drugs racked up more than $16 billion in sales, according to IMS Health, a firm that tracks drug trends for the health-care industry. For the past three years they have ranked near or at the top of the best-selling classes of drugs, outstripping antidepressants and sometimes cholesterol medicines. A study published last year found that off-label antipsychotic prescriptions doubled between 1995 and 2008, from 4.4 million to 9 million. And a recent report by pharmacy benefits manager Medco estimated that the prevalence of the drugs’ use among adults ballooned more than 169 percent between 2001 and 2010.
Critics say the popularity of atypical antipsychotics reflects a combination of hype that the expensive medicines. designed to calm patients and to moderate the hallucinations and delusions of psychosis, are being used “promiscuously, recklessly,” often to control behavior and with little regard for their serious side effects. These include major, rapid weight gain — 40 pounds is not uncommon — Type 2 diabetes, breast development inboys, irreversible facial tics and, among the elderly, an increased risk of death.
Step-by-step explanation:
Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and haloperidol have been called typical or first generation. They cause both antipsychotic actions and many side effects (extrapyramidal and endocrine) that are ascribed to their high affinity dopamine D2 receptor antagonism. Drugs such as clozapine, olanzapine, risperidone and others were then developed that avoided the neurological side effects (atypical or second generation antipsychotics). These compounds are divided mechanistically into those that are high affinity D2 and 5-HT2A antagonists, and those that also bind with modest affinity to D2, 5-HT2A, and many other neuroreceptors. There is one approved third generation drug, aripiprazole, whose actions have been ascribed alternately to either D2 partial agonism or D2 functional selectivity. Although partial agonism has been the more widely accepted mechanism, the available data are inconsistent with this mechanism. Conversely, the D2 functional selectivity hypothesis can accommodate all current data for aripiprazole, and also impacts on discovery compounds that are not pure D2 antagonists.The serendipitous observations about antipsychotic actions of chlorpromazine ultimately led to the finding that these antipsychotic effects were due to antidopaminergic actions [2]. Numerous antipsychotics were subsequently developed that, like chlorpromazine, work primarily as dopamine D2 receptor antagonists. Drugs of this type (first called typical and now named first generation antipsychotics) include a variety of different chemical classes. These typical drugs can be classified as high, intermediate, or low potency based on their average daily dose range, with their clinical potency often highly correlated with their affinity for the dopamine D2 receptor . Thus, actions at dopamine systems have been a critical mechanism in all currently approved antipsychotic drugs and many of the compounds in the discovery and development pipeline.The serendipitous observations about antipsychotic actions of chlorpromazine [1] ultimately led to the finding that these antipsychotic effects were due to antidopaminergic actions . Numerous antipsychotics were subsequently developed that, like chlorpromazine, work primarily as dopamine D2 receptor antagonists. Drugs of this type (first called typical and now named first generation antipsychotics) include a variety of different chemical classes. These typical drugs can be classified as high, intermediate, or low potency based on their average daily dose range, with their clinical potency often highly correlated with their affinity for the dopamine D2 receptor. Thus, actions at dopamine systems have been a critical mechanism in all currently approved antipsychotic drugs and many of the compounds in the discovery and development pipeline.