Hallucinogens, mechanism of action, Difference between 2A agonists and 2A agonists that are hallucinogens Options

[Orbz]

Gonzalez-Maeso et al (2007)
Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior
Neuron 53;3, 439-452

The study looked at 5-HT2A agonists which are hallucinogens and 5-HT2A agonists which are not. The difference is in the down stream signalling.

While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric Gi/o proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens.

Might this also be the difference betwen atypical and typical antipsychotics causing neurloeptic malignant syndrome? Typical antipsychotics induce second messengers through D2 receptors which atypicals don't?

[Maykel Abdelmessih]

Gonzalez-Maeso et al (2007)
Hallucinogens recruit specific cortical 5-HT2A receptor-mediated signaling pathways to affect behavior
Neuron 53;3, 439-452

The study looked at 5-HT2A agonists which are hallucinogens and 5-HT2A agonists which are not. The difference is in the down stream signalling.



While lisuride and LSD both act at 2AR expressed by cortex neurons to regulate phospholipase C, LSD responses also involve pertussis toxin-sensitive heterotrimeric Gi/o proteins and Src. These studies identify the long-elusive neural and signaling mechanisms responsible for the unique effects of hallucinogens.


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I agree, this is why typical antipsychotics are not as good as LSD. just LSD affecting large number of Gprotien receptors and adrenoreceptors and binding to most seratonin receptors increasing glutamate release and excitation, Also it's action in DARPP-32 gene will definitely block action potentials activity in the brain stem.



Might this also be the difference betwen atypical and typical antipsychotics causing neurloeptic malignant syndrome? Typical antipsychotics induce second messengers through D2 receptors which atypicals don't?

I think that atypicals are more selective to 5HT-2A, and 5HT1A, where that typicals are not selective , just bocking D2 receptors in different pathways other than mesolimbic and nigrostriatal pathway in long term has the potential in giving NMS
In addition if primary cause if NMS also has genetic factors that causes this neuromalignant syndrome, reduced levels of dopamine receptors and this will raise levels of creatine phosphokinase in plasma and get increase in muscle activity and shift in congitive pattern. I don't think that people would go nuts or anything though.

what about the Tardive dyskinesia syndrome, in terms of the dopaminc receptor bockage mechanism, is it similar to the way atypicals drugs also affect the seratonin receptors?