First-Generation Antipsychotics (FGAs)
FGAs are primarily dopamine antagonists, blocking the action of dopamine on its receptors throughout the brain. One of the theoretical causes of schizophrenia is excess dopamine in the mesolimbic pathways, which is associated with positive symptoms; hence, blocking this pathway aids in alleviating positive symptoms like hallucinations and delusions. However, FGAs are not specific to D2 receptors and exhibit their action on a number of other receptors, resulting in a varied side effect profile. This includes exerting antagonism at Acetylcholine ACh M1, Histamine H1 antagonist and a1-adrenergic receptors.
| Effect of First-Generation Antipsychotics on D2 receptors | ||
| D2 receptor in mesolimbic pathway | D2 receptor in Nigrostriatal Pathway | D2 receptor in tuberoinfundibular pathway (hypothalamus/pituitary) |
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| Additional receptor profile of First Generation Antipsychotic | ||
| Muscarinic | Histamine | Adrenergic |
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Source: Adapted from: UpToDate. First Generation Antipsychotic Medications: Pharmacology, administration and comparative side effects [internet]. 2022 [cited 2022 July 15]. Available from: https://www.uptodate.com/contents/first-generation-antipsychotic-medications-pharmacology-administration-and-comparative-side-effects
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