Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide potently and reversibly blocks alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR (IC(50)=6.9-54.9 nM), alpha-3-beta-2/CHRNA3-CHRNB2 (IC(50)=9.7-97.5 nM) and alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)=11.1-17.2 nM) (PubMed:15983035, PubMed:21252227, PubMed:22914547, PubMed:23846688, PubMed:32101438). It also inhibits alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR with a higher potency on human (IC(50)=6.75 nM) than on rat receptors (IC(50)=130-147 nM) (PubMed:22914547, PubMed:33523678). Also shows a weak ability to inhibit alpha-3-beta-4/CHRNA3-CHRNB4 (IC(50)=480-1500 nM) (PubMed:15983035, PubMed:22914547). This synthetic toxin also inhibits N-type calcium channels (Ca2.2/CACNA1B) (IC(50)=1.1 nM) via the activation of the G protein-coupled GABA(B) receptor in DRG neurons (PubMed:21252227). Also exhibits inhibition of D.melanogaster alpha-7 nAChRs (PubMed:25466886). Expressed by the venom duct. The cysteine framework is I (CC-C-C). Alpha4/7 pattern. The hydroxylation at position Pro-27 is critical, since an hydroxylation at this position decreases potency of the toxin to inhibit both alpha-3-beta-2 (1300-fold) and alpha-6/alpha-3-beta-2-beta-3 (130-fold) nAChRs. A non-modified residue at position Pro-34 is critical, since a hydroxylation at this position decreases potency of the toxin to inhibit alpha-3-beta-2 (1-45-fold) and increases potency to inhibit alpha-6/alpha-3-beta-2-beta-3 (1.77-fold) nAChRs. This toxin shows a very weak or no inhibition on mammalian muscle alpha-1-beta-1-gamma-delta, neuronal alpha-7, and neuronal alpha-4-beta-2 nAChR. The mutant [A28V, S30H, V31A, N32R, E35A] is >15'000-fold more potent at inhibiting alpha-6/alpha-3-beta-2-beta-3 than alpha-3-beta-2, and is essentially inactive on all other non-alpha6-containing nAChRs including alpha-3-beta-4, alpha-4-beta-2, alpha-4-beta-4 and alpha-7 (PubMed:23846688). This mutant shows inhibition on alpha-6/alpha-3-beta-2-beta-3 (IC(50)=3.8 nM), beta-3-alpha-6-beta-2-alpha-4-beta-2 (IC(50)=6.3 nM), alpha-3-beta-4 (IC(50)=3.7 uM), alpha-3-beta-2 (IC(50)=6.1 uM), beta-4-alpha-3-beta-4-alpha-3-alpha-5 (IC(50)=9.2 uM), and does not inhibit alpha-4-beta-2 and alpha-4-beta-4 nAChRs (PubMed:26330550). The mutant [S30H, V31A, E35N] is >290-fold more potent at inhibiting alpha-6/alpha-3-beta-2-beta-3 than alpha-6/alpha-3-beta-4, demonstrating that it can discriminate between alpha-6-beta-2-beta-3 and alpha-6-beta-4 nAChRs. The mutant PeIA-5667 [A28V, S30N, N11R, L36I] is much more potent at inhibiting alpha-6/alpha-3-beta-4 nAChR than the wild-type toxin on both rat (IC(50)=0.20 nM) and human channels (IC(50)=0.48 nM). It shows moderate activity on alpha-3-beta-4 nAChR (IC(50)=179-230 nM on rat and human channels) and on alpha-6/alpha-3-beta-2-beta-3 nAChR (IC(50)=111-135 nM on rat and human channels). It does not show activity on all other channels tested. Belongs to the conotoxin A superfamily.