The mechanism is commonly thought to depend on decreased levels of dopamine activity due to: * Dopamine receptor blockade * Genetically reduced function of dopamine receptor D2 It has been proposed that blockade of D2-like (D2, D3 and D4) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity. Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5HT1 receptors by certain of them reduces GABA release and indirectly induces glutamate release, worsening this<unk> . The muscular symptoms are most likely caused by blockade of the dopamine receptor D2, leading to abnormal function of the basal ganglia similar to that seen in Parkinson's disease. However, the failure of D2 dopamine receptor antagonism, or dopamine receptor dysfunction, do not fully explain the presenting symptoms and signs of<unk> , as well as the occurrence of<unk>  with atypical antipsychotic drugs with lower D2 dopamine activity. This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as a mechanism for<unk> . Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in the breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical<unk> s, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to<unk>  present themselves. There is also thought to be considerable overlap between<unk>  catatonia and<unk>  in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same<unk> . The raised white blood cell count and creatine phosphokinase (CPK) plasma concentration seen in those with<unk>  is due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue). The patient may suffer hypertensive crisis and metabolic acidosis. A non-generalized slowing on an EEG is reported in around 50% of cases. The fever seen with<unk>  is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the high white blood cell and CPK count) are caused by the antipsychotic drugs. They cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.
Neuroleptic malignant syndrome
Malignant hyperthermia
Limbic encephalitis
Catatonia
Viral encephalitis
Serotonin syndrome
Oculogyric crisis
Heat stroke