Selectivity for Insect versus Vertebrate nAChRs

Neonicotinoid insecticides are more than 100-fold selective for insect nAChRs over vertebrate nAChRs, but little is known about the mechanism of selectivity 

Debnath and coworkers [153] have demonstrated, in a QSAR study performed using electrotopological state atom indices, that compounds with a [=N-N02] (e.g., 7, 10, 12, 13 and 14), [=CH-N02] (e.g., 8) or [=N-CN]-pharmacophore (e.g., 9 and 11) are more active, selectively, to Drosophila nAChR and safe for humans, whereas N-unsubstituted imines having affinity to mammalian receptor. 

It has been shown that two important enzymes in metabohsm of neonicotinoids, the liver microsomal CYP3A4 (mainly oxidation of imidazolidine moiety) 

In contrast to S-(—)-nicotine (1 rat oral LD50 = 50-60 mg a.i. kg , high mammalian oral and dermal toxicity), neonicotinoid insecticides display excellent selectivity profiles that are largely attributable to spedfity for insect versus vertebrate nAChRs. This is exemplified by the fact that the radioligand [ H]-7 serves 

Neonicotinoid lnsectl l IC50 (nM) vertebrate a4/j2l I Selectivity ratio 

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