posted May 20, 2014 12:06 PM            

Basically this study shows that competitive non-inactivating antagonists at the 5-ht7 receptor are able to reverse and reactivate the receptor after Risperdone induced irreversible wash-resistant inactivation at the 5-ht7 receptor.

Competitive non-inactivating 5-ht7 antagonists includes Mianserin and Cyproheptadine.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052287/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033711/

Competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions.

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Abstract
RATIONALE:
The h5-HT(7) receptor is subject to inactivation by risperidone and 9-OH-risperidone, apparently through a pseudo-irreversible complex formed between these drugs and the receptor. Although risperidone and 9-OH-risperidone ("inactivating antagonists") completely inactivate the receptor, only 50% of the receptors form a pseudo-irreversible complex with these drugs.
OBJECTIVES:
This study aims to more fully determine the mechanism(s) responsible for the novel effects of risperidone and 9-OH-risperidone and to determine if the inactivation can be reversed (reactivation).
METHODS:
The ability of non-inactivating drugs (competitive antagonists) to dissociate wash-resistant [(3)H]risperidone binding from h5-HT(7) receptors was investigated. Also, the ability of non-inactivating drugs to reactivate inactivated h5-HT(7) receptors was investigated, using cAMP accumulation as a functional endpoint.
RESULTS:
The competitive (non-inactivating) antagonists clozapine and mesulergine released the wash-resistant [(3)H]risperidone binding to the h5-HT(7) receptor. The competitive antagonists clozapine, SB269970, mianserin, cyproheptadine, mesulergine, and ICI169369 reactivated the risperidone-inactivated h5-HT(7) receptors in a concentration-dependent manner. The potencies for reactivation closely match the affinities of these drugs for the h5-HT(7) receptor (r(2) = 0.95), indicating that the reactivating antagonists are binding to and producing their effects through the orthosteric binding site of the h5-HT(7) receptor. Bioluminescence resonance energy transfer analyses indicate that the h5-HT(7) receptor forms homodimers.
CONCLUSIONS:
The ability of the non-inactivating drugs to bind h5-HT(7) orthosteric sites and reverse the wash-resistant effects of risperidone or 9-OH-risperidone, also bound to h5-HT(7) orthosteric sites, is evidence for protomer-protomer interactions between h5-HT(7) homodimers. This is the first demonstration of a non-mutated G-protein-coupled receptor homodimer engaging in protomer-protomer interactions in an intact cell preparation.

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posted May 20, 2014 05:54 PM            

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Originally posted by Ellynlvx:
At the risk of sounding like a complete imbecile here, Aries, please translate...

(Now I know how all those people I speak Astrologese to feel.)

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posted May 21, 2014 10:49 AM            

Okay, now I understand.

Phew!