Antipsychotics, also termed neuroleptics (derived from Greek; Neuro meaning nerve, and lepsis, meaning to take hold) are classified into two groups, typical and atypical. The choice of drug prescribed is highly dependent on the patient, and due to the advent of atypical antipsychotics, which tend to have the same effect as the typical antipsychotics but with reduced side effects, the typical drugs only tend to be used when atypical drugs are not effective. The balance between negative and positive symptoms varies greatly with each patient, and this can influence the effects of each drug.
Typical antipsychotics (or first-generation antipsychotics) were discovered in the 1950s. Clorpromazine, the first typical antipsychotic, was discovered for its anaesthetic actions in around 1947, before being marketed as a psychiatric drug. It was the prototype antipsychotic, of which the rest of the Phenothiazine antipsychotics were derived. Chlorpromazine's chemical structure is illustrated in the image to the right. As well as the phenothiazine antipsychotics, there are also Butyrophenone and Thioxanthene antipsychotics. There is an outline of these groups below:
The largest group of typical antipsychotics, which includes Chlorpromazine. These drugs also have an anti-nausea and anti-vomiting effect. Along with Promazine, Triflupromazine, and Levomepromazine, Chlorpromazine has a moderate autonomic effect and so moderate severity of side effects. They do however have a strong sedative effect.
Fluphenazine, Perphenazine, Flupentixol, Prochlorperazine and Trifluoperazine are all very potent phenothiazine antipsychotics, and therefore tend to have relatively severe side effects. Fluphenazine for example, is around 70 times more potent than chlorpromazine.
The butyrophenones are generally more potent than the phenothiazines. Haloperidol for example is 50 times more potent than chlorpromazine. It is particularly effective against the positive symptoms of schizophrenia of delusions and hallucinations. Other butyrophenones Triperidol and Benperidol are 100 and 200 times more potent than Chlorpromazine respectively. In fact, Benperidol is the most potent antipsychotic on the market.
This class of typical antipsychotics are closely related to the phenothiazines, and therefore have some of the same side effects. Some examples of thioxanthene antipsychotics include: Flupenthixol, Chlorprothixine, Thiothixine and Zuclopenthixol.
Atypical, or second-generation antipsychotics were discovered later than typical antipsychotics and tend to have less side effects, although this is somewhat debated. Clozapine (not to be confused with the typical antipsychotic chlorpromazine) was discovered around the same time as the typical antipsychotics (1961) but was only brought into clinical use in the middle of the 1970s. Clozapine was however withdrawn in 1975 due to its tendency to cause fatal agranulocytosis. It was later reintroduced in the treatment of schizophrenia where other treatments showed minimal effects, as it is more effective in reducing positive and negative symptoms. Clozapine's chemical structure is shown to the right, note its similarity to chlorpromazine's structure at the top of the page. Most of the other atypical antipsychotics were introduced in the 1990s.
Atypical drugs tend to be unrelated, and classification of an antipsychotic as atypical seems to be somewhat dependent on each individual case. However, most atypicals have some form of action on serotonin receptors as well as dopamine receptors. One such atypical antipsychotic is Risperidone, introduced shortly after Clozapine in the 1990s. Risperidone is one of the only drugs available for the treatment of younger patients with schizophrenia, although this has recently been featured in the news, outlining the risks involved in giving the drug to children under the age of 12 due to the continuing development of the young brain. Quetiapine and Ziprasidone were also introduced around this time.
More recently, Aripiprazole was introduced, which varies from other atypical antipsychotics as it is a dopamine and serotonin partial agonist. Paliperidone was the latest atypical antipsychotic to be introduced in 2006, and Asenapine and Iloperidone are currently under review for approval.
Other drugs in the treatment of schizophrenia are not classified as antipsychotics but some appear to have the same mechanism of action. For example, Tetrabenazine is similar in that it increases degradation of dopamine. Interestingly, it is also useful as a treatment for tardive dyskinesia, a side effect of many antipsychotics.
Surprisingly, a promising alternative treatment for schizophrenia has been discovered in cannabis. Cannabidiol, a chemical in the plant has been shown to have antipsychotic properties without any of the side effects of typical or atypical antipsychotics, even at high doses.
A table illustrating various properties of some antipsychotic drugs can be found on the Table of Antipsychotics page.
Links to information on antipsychotic drugs and their chemical properties:
NHS Choices Antipsychotics Drug Guide:
A very in depth guide to drugs available in the UK, including various dosages available and dose schedules, warnings, ingredients, and interactions with other drugs.
Scientifically-aimed database of drugs and their various chemical properties.
Similar to above link but a database of chemicals in general.
Wikipedia Antipsychotics Page:
Good overview-type information for many of the antipsychotics, although somewhat unstructured.
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