A rational ordering of the actions of antipsychotic drugs

Most major actions of the antipsychotic drugs stem from one of the four antagonistic functions common to all these drugs. Antidopaminergic activity in the mesolimbic system results in the primary desired effect, control of psychosis. Antidopaminergic activity also occurs in other brain areas. Dopamine blockade in the nigrostriatal pathway results in extrapyramidal symptoms and tardive dyskinesia. Blockade in the tuberoinfundibular tract of the hypothalamus causes elevated circulating prolactin. Central H1 histaminic receptors are also blocked by these drugs, causing sedation. The anti-alpha adrenergic activity of the antipsychotics results in orthostatic hypotension, and antimuscarinic activity results in the atropinic picture commonly seen with these drugs. The mnemonic "the anti-fours" is used to order the four major pharmacological effects: anti-dopaminergic, anti-H1 histaminic, anti-alpha adrenergic, and anti-muscarinic.