Compared to first-generation antipsychotics (FGAs), how does the imbalance between acetylcholine and dopamine manifest in second-generation antipsychotics (SGAs)?

The imbalance between acetylcholine and dopamine is indeed less pronounced in second-generation antipsychotics (SGAs) compared to first-generation antipsychotics (FGAs). This difference is primarily due to the pharmacological profiles of the two classes of medications.

SGAs are designed to target both dopamine and serotonin receptors, which is thought to contribute to their improved efficacy in treating negative symptoms of schizophrenia and reducing the incidence of extrapyramidal side effects (EPS) that are more commonly associated with FGAs. The lower incidence of EPS in SGAs is partly due to their ability to reduce the imbalance between dopamine and acetylcholine, an issue that FGAs often exacerbate due to their stronger antagonistic effects on dopamine receptors without a compensatory effect on acetylcholine levels.

By having a more nuanced impact on various neurotransmitter systems, SGAs mediate dopamine activity while also influencing serotonin pathways, thereby creating a more balanced neurochemical environment. This results in fewer extrapyramidal symptoms and overall a more tolerable side effect profile, making SGAs a preferred choice for many patients in managing psychotic disorders.