19.02.6 Typical Antipsychotics (First Generation)

Typical antipsychotics comprise a number of different types of chemicals, including chlorpromazine, and haloperidol). Both of these drugs ameliorate the positive (psychotic) symptoms of schizophrenia but have little effect on negative and cognitive symptoms. These drugs, in addition to being potent D₂ receptor antagonists demonstrating up to 80% occupancy at therapeutic doses, show moderate potency at α-adrenergic, 5-HT₂, muscarinic acetylcholine, and histamine receptors at therapeutic doses (except haloperidol which is highly selective for D₂ receptors).

As they block many receptors, the typical antipsychotics, have numerous anticholinergic (dry mouth, blurred vision, constipation), antihistaminergic (sedation, drowsiness), adrenergic (cardiac side effects, hypotension) and serotoninergic (weight gain) side effects. The most severe side effects with these drugs, however, occur through their target dopamine receptors. By blocking dopamine transmission in the nigrostriatal pathway, antipsychotic drugs cause movement disorders such as tardive dyskinesia (loss of voluntary control of movements which is debilitating and may not remit following drug cessation), parkinsonism (tremor, shuffling gait, cogwheel rigidity etc.), disordered muscle tone and motor restlessness. Blocking dopamine transmission in the tuberinfundibular pathway causes elevated prolactin secretion from the pituitary gland, leading to enlarged breasts, weight gain, erectile dysfunction and menstrual irregularities. The extent and severity of side effects incurred with typical antipsychotic drugs limits their effectiveness as patients are less likely to comply with treatment.