This toxin target two types of receptors, the nicotinic acetylcholine receptor (nAChR) and the G-protein-coupled receptor GABA(B). It specifically inhibits the alpha-9-alpha-10/CHRNA9-CHRNA10 nAChR, with preference for rat receptors (PubMed:16445293, PubMed:21888386, PubMed:22774872, PubMed:25740413, PubMed:28223528, PubMed:18242183, PubMed:18295795). It interacts with the alpha-10(+)/alpha-9(-)interface of the receptor (PubMed:25740413). It shows a two order of magnitude species difference potency for the rat versus human alpha-9-alpha-10 nAChR, due to the Thr-86 located in the alpha-9 nAChR subunit (PubMed:22774872). This toxin also shows inhibition of high voltage-activated (HVA) calcium channels (Cav2.2) by acting on GABA(B) receptors (GABBR1 and GABBR2) (PubMed:18945902, PubMed:21888386). In vivo, this toxin produces an acute antinociceptive effect in peripheral nerve-injured rats, which may be related to the inhibition of immune cell buildup at the site of nerve injury (PubMed:17101979). In addition, when intramuscularly injected into rats following chronic constriction injury of the sciatic nerve, this toxin protects peripheral nervous tissues as well as prevents central maladaptive plasticity by inhibiting glial cell activation (PubMed:25008370). Expressed by the venom duct. The cysteine framework is I (CC-C-C). Alpha4/3 pattern. The disulfide bond CysI-CysIII is important for alpha-9-alpha-10 subtype inhibition, whereas the bond CysII-CysIV contributes to GABA(B) modulation. The derivative RgIA4 (S23T; R28Citrulline; Y29(3-I-Y); R30Q; R32Y) is under preclinical studies by Kineta under the name KCP-400. It is tested to prevent chronic cancer chemotherapy-induced neuropathic pain. RgIA[Del13]dimer is an analog therapeutically interesting because it is the first dual inhibitor that potently and selectively inhibits alpha-9-alpha-10/CHRNA9-CHRNA10 and alpha-7/CHRNA7 subtypes, which are both involved in the etiology of several cancers. This toxin shows a weak activity on alpha-7 nAChR (IC(50)=3310-4660 nM) (PubMed:16445293, PubMed:18295795). It also shows a very weak activity on alpha-2-beta-2, alpha-2-beta-4, alpha-3-beta-4, alpha-3-beta-2, alpha-4-beta-2, alpha-4-beta-4 and alpha-6/alpha-3-beta-2-beta-3 nAChRs (IC(50)>10 uM) (PubMed:16445293). The cis-[2,8]-dicarba analog is significantly more stable and less susceptible to proteolytic degradation than native RgIA. Replacement of Arg-28 by a Citrulline residue strongly increases the potency on human CHRNA9-CHRNA10 nAChR. Replacement of Tyr-29 by a monoido-Tyr (3-I-Y) residue very strongly increases the potency on human CHRNA9-CHRNA10 nAChR. The synthetic variant RgIA4 (S23T; R28Citrulline; Y29(3-I-Y); R30Q; R32Y) is very potent on human CHRNA9-CHRNA10 (IC(50)=1.5 nM) and the most selective among all other synthetic variants tested (IC(50)>10 uM on all receptors tested, and (IC(50)=1.8 uM) on alpha-7/CHRNA9 nAChR). Belongs to the conotoxin A superfamily. Has the same mature sequence than Reg1e (AC P85011). RgIA could therefore be the precursor of Reg1e, except that RgIA does not have the C-terminal Gly residue required for C-terminal amidation of Reg1e.