Orphan Receptors

December 14, 2010 at 5:43 pm (Uncategorized)

If a drug changes the nervous system and hence our behavior, it’s probably doing one of two things. Either it is a neurotoxin that damages nervous tissue, or it changes the activity of neurons.  Neurologists understand the mechanisms behind the well known drugs.  (Most stimulants affect dopamine. CNS depressants generally affect GABA receptors, narcotics affect opiate receptors, etc.)

These exogenous (coming for outside the body) compounds are better understood than their endogenous (produced by the body) counterparts. Neurons have receptors for various neurotransmitters, neuro-modulators, and hormones. Presumably these receptors are meant to be stimulated by endogenous compounds in the body. But it is often the case that scientists are unable to conclusively identify the compounds that psychoactive drugs mimic. Nerve cells are thus said to have orphan receptors. 

Perhaps a good place to start are the benzodiazepenes. (Xanax, Valium, Ativan, etc.) These drugs are GABA agonists (they increase the effectiveness of the mind’s no. 1 inhitory neurotransmitter). There is a site on GABA receptors where the benzodiazpenes bind to, but to this author’s knowledge no conclusive endogenous compound has been found.

This puts scientists in something of a pickle. What, exactly, are these orphan receptors for? Some time ago opiate receptors were orphans. This lead to the discovery of the familiar endorphins, which seem to be released as a reward for certain types of behavoir, such as active exercise and sex. What activity would the benzodiazapene by trying to inhibit when it binds to GABA receptors, and where does it come from? The answers (to both benzodiazipine receptor sites and orphan receptors in generally) should help us understand more about our minds and bodies, and this is only one of the orphan receptors found in the brain. Research into any receptors has serious potential for new medicine.

(Note, after finishing this entry I came across another interesting fact. A previous orphan receptor, the cannibanoid receptor, has an antagonist, cannabidiol. It blocks the cannabinoid receptors and is being looked at as a potential antipsychotic. Bizarrely enough, it coexists with THC in the cannabis plant. )


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