Receptor affinities that tend to appear together.

[atara]

I've noticed two curiosities:

First, NMDA antagonists tend to also be nicotinic acetylcholine antagonists. This is true of ketamine, dextromethorphan, ibogaine, nitrous and phencyclidine.

Second, GABA-A benzodiazepine site modulators tend to also be adenosine reuptake inhibitors. This is true of benzos, barbs, soma, and alcohol.

Is there a reason for this, or is it just coincidence?

Also, the D2 receptor seems neglected. PCP, Salvia, Ketamine, and LSD all have nontrivial D2 affinity, but this is rarely mentioned.

 

[Nexus298]

I've noticed this as well but my thoughts on it were that its just coincidence that 2 different acting receptors are apparently shaped similarly. Like 5HT2a and 5HT2c they do different things but frequently attract the same chemicals. GHB and GABAb are two that are contradictory as well, I don't have the link but I remember reading GHB receptors were responsible for seizures in overdoses, which contradicts the GABAb receptor. I do think there is relationships between NMDA antaganist and opiate receptors though. We don't fully understand them yet though.

 

[mad_scientist]

Kappa and sigma agonist effects also tend to correlate together, along with NMDA antagonist effects often enough. As said above the receptors probably just have similar shapes, maybe by coincidence (in the case of sigma and kappa for instance, which share little sequence homology) but more likely in most cases the different receptors are derived from gene duplication events back in evolutionary history, so they are only different because of a few point mutations at the active site that have arisen over time.

 

[michael_1992]

antihistamines usually also block the muscarinic acetylcholine receptors. the receptors are probably just very similar in structure

 

[MurphyClox]

^Both are GPCRs, so Mad_Scientist's explanation applies again.

For further details see e.g.:

Holger Römpler, Claudia Stäubert, Doreen Thor, Angela Schulz, Michael Hofreiter, Torsten Schöneberg
"G Protein-Coupled Time Travel: Evolutionary Aspects of GPCR Research"
Molecular Interventions 2007, 7(1), p.17
DOI: 10.1124/mi.7.1.5

Abstract
The common seven-transmembrane–domain (TMD) architecture of G protein–coupled receptors (GPCRs) has been preserved over a vast period of time, and highly conserved amino acid motifs and residues have evolved to establish ligand and signal transduction specificities. The mining of evolutionary data from sequenced genomes and targeted retrieved orthologs has proven helpful for understanding the physiological relevance of individual GPCRs and for interpreting the clinical significance of GPCR mutations in structural terms. Sequence analysis of GPCR pseudogenes, which are considered as genomic traces of past functions, as well as recent success in sequence analysis of GPCR genes from extinct species, provide further information. This review discusses recent advances and approaches aimed at developing a better understanding of GPCR biology based on evolutionary data.

Full access is free!


Peace! - Murphy

 

[seep]

Also, the D2 receptor seems neglected. PCP, Salvia, Ketamine, and LSD all have nontrivial D2 affinity, but this is rarely mentioned.

It's mentioned by pharmaceutical companies as part of their proofs of concept for novel antipsychotics.

I've also seen many people confuse effect for affinity quite often, especially when one biological process exerts control over another process. For instance, miosis (pupil constriction) is the effect of cholinergic activity, but the relationship between morphine and acetylcholine receptors is complex.