Dopamine 2 antagonists
Dopamine 2 receptors antagonists
D2 antagonists are utilized as antipsychotic agents as they block post-synaptic D2 receptors. As can be seen in the graphic, their effects are seen over all dopaminergic pathways. Thus, patients will not only have a decrease in psychosis, but an increase in prolactin secretion (often leading to gynaecomastia), the emergence of Parkinson's-like symptoms, and a decrease in concentration. Recently the risk of antipsychotics contributing to the worsening of patient's lipid profiles, increasing serum glucose and prolonging QT intervals has come to light. One rare, but potentially fatal side effect is the neurological disorder Neuroleptic Malignant Syndrome (NMS).
Note: neuroleptic is an older word for antipsychotics. In NMS, patients can present with muscle rigidity, high fever, fluctuating blood pressure and a change in cognitive function. NMS can occur from hours to months after initiation of an antipsychotic, and can rapidly progress to life-threatening within days. Patients who present with these symptoms should be admitted to hospital and observed for the need of supportive care: e.g. circulatory and ventilatory support, dantrolene for severe hyperthermia, and bromocriptine as an attempt to reverse the syndrome.
Haloperidol is considered a very specific D2 antagonist, therefore it is unlikely to cause any change in prolactin levels.
Extra info: Because D2 specific antagonists can work throughout the dopaminergic system, hyperprolactemia is likely with haloperidol.
Without D2 antagonism activity, a drug is NOT an antipsychotic.
Extra info: At this point in drug development, this statement appears to be true.
The relative activity of D2 antagonism can be altered with 5-HT2A and ACH antagonism.
Extra info: The adverse effects of antipsychotics in the nigrostriatal tract can be offset with the co-administration of either 5HT2A antagonist or a muscarinic antagonist.
It is possible for antipsychotic drug to target D2 receptors in specific dopaminergic tracts.
Giving an antipsychotic to a Parkinson’s patient with hallucinations can cause a worsening of Parkinson’s symptoms.
Extra info: Unfortunately, many patients with Parkinson's will develop psychosis, therefore a slow titration of any trial with an antipsychotic is warranted.