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OCD primarily involves the brain regions of the striatum and the cingulate cortex, especially the striatum. OCD involves several different receptors, mostly H2, M4, nk1, NMDA, and non-NMDA glutamate receptors. The receptors 5-HT1D, 5-HT2C, and the mu opioid receptor exert a secondary effect. The H2, M4, nk1, and non-NMDA glutamate receptors are active in the striatum, whereas the NMDA receptors are active in the cingulate cortex.

The activity of certain receptors is positively correlated to the severity of OCD, whereas the activity of certain other receptors is negatively correlated to the severity of OCD. Those correlations are as follows:

Activity positively correlated to severity:

  • H2
  • M4
  • nk1
  • non-NMDA glutamate receptors

Activity negatively correlated to severity:

  • NMDA
  • mu opioid
  • 5-HT1D
  • 5-HT2C

The central dysfunction of OCD involves the receptors nk1, non-NMDA glutamate receptors, and NMDA, whereas the other receptors exert secondary modulatory effects.

Pharmaceuticals that act directly on those core mechanisms are aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin (NMDA receptor sensitizer). The drugs that are popularly used to fight OCD lack efficacy because they do not act upon the core mechanisms.

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