Mechanism of Action - Psychopharmacology

Mechanism of Action

The major action of all antipsychotics in the nervous system is to block receptors for the neurotransmitter dopamine; however, the therapeutic mechanism of action is only par-tially understood. Dopamine receptors are classified into subcategories (D1, D2, D3, D4, and D5), and D2, D3, and D4 have been associated with mental illness. The typical antipsychotic drugs are potent antagonists (blockers) of D2, D3, and D4. This makes them effective in treating target symptoms but also produces many extrapyramidal side effects (discussion to follow) because of the blocking of the D2 receptors. Newer, atypical antipsychotic drugs, such as clozapine (Clozaril), are relatively weak blockers of D2, which may account for the lower incidence of extrapyrami-dal side effects. In addition, atypical antipsychotics inhibit the reuptake of serotonin, as do some of the antidepressants, increasing their effectiveness in treating the depressive aspects of schizophrenia. Paliperidone (Invega) is the new-est atypical antipsychotic, gaining approval for distribution in the United States in January 2007. It is chemically similar to risperidone (Risperdal); however, it is an extended-release preparation. This means the client can take one daily dose in most cases, which may be a factor in increased compliance.

A new generation of antipsychotics, called dopamine system stabilizers, is being developed. These drugs are thought to stabilize dopamine output; that is, they preserve or enhance dopaminergic transmission when it is too low and reduce it when it is too high. This results in control of symptoms without some of the side effects of other antipsy-chotic medications. Aripiprazole (Abilify), the first drug of this type, was approved for use in November 2002. In clini-cal trials, the most common side effects were headache, anxiety, and nausea.

Four antipsychotics are available in depot injection, a time-release form of medication for maintenance therapy. Two con-ventional antipsychotics use sesame oil as the vehicle for these injections, so the medication is absorbed slowly over time; thus, less frequent administration is needed to maintain the desired therapeutic effects. Prolixin (decanoate fluphenazine) has a duration of 7 to 28 days, and Haldol (decanoate haloperi-dol) has a duration of 4 weeks. After the client’s condition is stabilized with oral doses of these medications, administration by depot injection is required every 2 to 4 weeks to maintain the therapeutic effect. Risperidone (Risperdal Consta) Paliperi-done (Invega Sustenna), atypical antipsychotics, encapsulates active medication into polymer-based microspheres that degrade slowly in the body, gradually releasing the drug at a controlled rate. Risperdal Consta, 25 mg, is given every 2 weeks. Paliperidone (Invega Sustenna) 117mg is given every 4 weeks.