Which medications in the drug class Antipsychotics, 1st Generation are used in the treatment of Schizophrenia?

Updated: Mar 16, 2018
  • Author: Frances R Frankenburg, MD; Chief Editor: Glen L Xiong, MD  more...
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Answer

Antipsychotics, 1st Generation

First-generation (conventional or typical) antipsychotics, are strong dopamine D2 antagonists. However, each drug in this class has various effects on other receptors, such as serotonin type 2 (5-HT2), alpha1, histaminic, and muscarinic receptors.

First-generation antipsychotics have a high rate of extrapyramidal side effects, including rigidity, bradykinesia, dystonias, tremor, and akathisia. Tardive dyskinesia (TD)—that is, involuntary movements in the face and extremities—is another adverse effect that can occur with first-generation antipsychotics. Neuroleptic malignant syndrome (NMS) can occur with these agents.

Chlorpromazine

Chlorpromazine is a phenothiazine antipsychotic that is a dopamine D2 receptor antagonist. It was the first conventional antipsychotic developed and is still in wide use for treatment of schizophrenia. Chlorpromazine is available in oral tablets, syrup, and concentrate; as an injectable solution for intramuscular (IM) administration; and in suppository form.

Chlorpromazine is a low-potency medication and is associated with sedation and weight gain.

Fluphenazine (Modecate, Modecate Concentrate, Moditen)

Fluphenazine is a high-potency typical antipsychotic that blocks postsynaptic dopaminergic D1 and D2 receptors. It has some alpha-adrenergic and anticholinergic effects. It is available orally and in a depot formulation (fluphenazine decanoate). A short-acting IM injection is also available for acute agitation. Fluphenazine is clinically comparable to haloperidol, a first-generation antipsychotic with similar potency, route of administration, side effects, and efficacy.

Haloperidol (Haldol, Haldol Decanoate)

Haloperidol is a dopamine D2 antagonist noted for high potency and low potential for causing orthostasis. The drawback is the high potential for extrapyramidal symptoms or dystonia. Haloperidol can interact with CYP3A4 and CYP2D6 inhibitors and inducers. It also can interact with drugs that prolong QTc intervals. Haloperidol is available in tablets, as a liquid concentrate, in IM and intravenous (IV) forms, and in long-acting IM form for depot injection.

Perphenazine

Perphenazine is a phenothiazine antipsychotic that blocks postsynaptic dopaminergic receptors and has alpha-adrenergic blocking effects. It has slightly lower potency than haloperidol and it sometimes classified as a midpotency drug. It is available in an oral formulation.

Thiothixene

Thiothixene is a dopamine D2 antagonist with anticholinergic and alpha-blocking effects. It is rarely used in the United States now.

Trifluoperazine

Trifluoperazine is a piperazine phenothiazine agent that is an antagonist at the postsynaptic mesolimbic dopaminergic D2 receptors.

Loxapine inhaled (Loxitane)

Loxapine's mechanism of action is unknown but probably involves antagonism of central dopamine D2 and serotonin 5-HT2A receptors. The inhaled dosage form is indicated for acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

Inhaled loxapine is a first-generation agent that may be similar to second-generation agents. In a new formulation, it can be inhaled, which may make it attractive for some patients.

Loxapine inhaled is the first noninjectable therapy to treat acute agitation associated with schizophrenia and bipolar I disorder. Approval by the US Food and Drug Administration (FDA) was based on 2 phase III studies of 658 individuals.


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