MAOIs: Multiple Effects and Sites of Action

Re^2: Symposium 524

Rita Raddatz

The possible connection between the "MAO inhibitor displaceable quinpirole binding site" (MQB) and I2 imidazoline binding sites is very interesting to me.  

I agree that interaction of I2 ligands (at < micro-molar concentrations) with the MAO-A/B active site should be discounted. However, these ligands do interact with high affinity (10-100 nM) with a distinct site on MAO. Interestingly, [3H]idazoxan binds with lower affinity to this site on human MAO-A than to the I2 site on human MAO-B. At concentrations used in radioligand binding assays it is likely that 3H-idazoxan is predominantly identifying the I2 site on MAO-B, (unless there are species differences). So, displacement of [3H]-idazoxan by clorgyline is especially interesting to me.

I'd be very interested in the experiment you suggested using BFI. Alternatively, if a site related to the imidazoline binding site on MAO-A is involved, amiloride could be useful (although it has other actions).

I'd be very interested in you thoughts on all this!

best wishes!

On Thu Dec 10, Kirsten Culver wrote
>Imidazoline receptors can be subdivided into I1 and I2 receptors. They occur both in brain and liver tissues, however for the purpose of my study, I am interested in brain I2 sites, since clorgyline has a high affinity for this receptor.

>In rat brain, imidazoline I2 receptors are located on the mitochondrial outer membrane and their distribution correlates well with the enzyme MAO-B. Morevover, it has been found that chronic clorgyline administration results in a downregulation I2 binding sites in rat brain cortex. Although these findings suggest some relationship between the enzyme MAO and the I2 site, a direct interaction of imidazoline ligands with the active centre of MAO-A/B has been discounted.

>Since clorgyline has a high affinity for the I2 site and moclobemide does not demonstrate any affinity for this site, it is possible that clorgyline's blockade of locomotor sensitization to quinpirole may be attributed to an action at this site.  Therefore,  if chronic clorgyline adminstration blocks quinpirole-induced locomotor sensitization via an activity at the I2 site, then it would be expected that chronic treatment with the I2 receptor ligand 2-BFI would also block locomotor sensitization to quinpirole.

>I'm glad you liked the poster!  


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