Atypical antipsychotic drugs atypicality defined

Clozapine is the prototype of atypical antipsychotic drugs, and it has been used effectively to treat patients with schizophrenia who are unresponsive or intolerant to typical antipsychotics [7]. Clozapine is characterized as atypical by its preferential binding to serotonin (5-HT2) and dopamine D4 receptors (D4) relative to dopamine D2 receptors [8]. A recent body of work also suggests that atypicality may be defined by the rate at which clozapine dissociates from D2 receptors. Specifically, clo-... 

From a clinical perspective, an atypical antipsychotic, however, is defined in part by the clinical properties that distinguish such drugs from conventional antipsychotics, namely, low extrapyramidal symptoms and efficacy for negative symptoms. By understanding the difference between blocking dopamine D2 receptors alone... 

The first of the second-generation, or atypical, antipsychotics was clozapine. Clozapine (Clozaril) is relatively free of the movement disorders that characterize the first-generation drugs. This is true of, and defines, second-generation, atypical antipsychotics. It was a significant breakthrough for schizophrenia patients. 

Several newer antipsychotic medications have been developed that seem different or atypical, compared with their predecessors. These agents include clozapine (Clozaril), risperidone (Risperdal), and several others listed in Tables 8-1 and 8-2. Although there is some debate about what exactly defines these drugs as atypical, the most distinguishing feature is that they have a much better side-effect profile, including a decreased risk of producing extrapyramidal (motor) side effects.17,45,57... 

Key CPZ equiv dose = Chlorpromazine equivalent dose.This concept is of value in comparing the potency of classical antipsychotics. Dose ranges are not specified as they are extremely wide and drugs are normally titrated up from low starting doses (e.g. chlorpromazine 25 mg or equivalent) until an adequate antipsychotic effect is achieved or the maximum dose reached.The chlorpromazine equivalent dose concept is of less value for atypical antipsychotics since minimum effective doses (Min. eff. dose) and narrower therapeutic ranges have been defined. Maximum dose (Max. dose) can be exceeded only under specialist supervision. 

Grunder G, Hippius H, Carlsson A (2009) The atypicality of antipsychotics a concept re-examined and re-defined. Nat Rev Drug Discov 8 197-202... 

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