Alkaloids including galanthamine (1) and codeine (2) are reported to be positive allosteric modulators of nicotinic acetylcholine receptors (nAChRs), but the binding sites responsible for this activity are not known with certainty. Analogues of galanthamine (1), codeine (2), and morphine (3) with reactivity towards cysteine thiols were synthesized including conjugated enone derivatives of the three alkaloids 4–6 and two chloro-alkane derivatives of codeine 7 and 8. The stability of the enones was deemed sufficient for use in buffered aqueous solutions, and their reactivity towards thiols was assessed by determining the kinetics of reaction with a cysteine derivative. All three enone derivatives were of sufficient reactivity and stability to be used in covalent trapping, an extension of the substituted cysteine accessibility method, to elucidate the allosteric binding sites of galanthamine and codeine at nAChRs.