Receptors schizophrenia

NMDAR1 receptor Schizophrenia SNPs in coding region, but no functional significance 14... 

Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach. 1998. Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin 24 189-202. 

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Its activity at Di receptors has been put forward as a possibility and although it has a relatively higher affinity for Di than Dj receptors, compared with typical neuroleptics, it is still a weak antagonist at both and in the absence of evidence for Di (or D5) receptor involvement in schizophrenia the significance of any Di antagonism is unclear. 

K (nM) values for clozapine at D2 and Di receptors are 56 and 141 compared with 0.5 and 27 for haloperidol giving D1/D2 ratios of 2.5 and 54 for the two drugs. A relatively strong block of Di compared with D2 receptors may not be the answer for schizophrenia but it could reduce the tendency to produce dyskinesias, if this depends on Di receptor activation (see Fig. 17.2). 

Some neuroleptics, including clozapine, are potent 5-HT-receptor antagonists and the possible role of 5-HT in the action of neuroleptics and the development of schizophrenia has recently generated much interest (Busatto and Kerwin 1997). This has centred primarily on 5-HT2A receptors found in the limbic cortex, which are linked to neuronal excitation and believed to mediate the hallucinogenic effects of drugs such as lysergic acid diethylamide (LSD). 

PET studies have almost always centred on measurements of binding and DA receptor number in the striatum rather than other DA-innervated areas of more significance in schizophrenia. Also in PM measurements of receptor number it is invariably the striatum which is used, because of its high density of DA receptors. 

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