IC50: 1.3 μM for α2β2, 2.3 μM for α2β4, 0.41 μM for α3β2, 23.1 μM for α3β4, 0.37 μM for α4β2, and 0.19 μM for α4β4 [1]
Dihydro-β-erythroidine hydrobromide (DHβE), the hydrogenated derivative of erythroidine, is a competitive antagonist of neuronal nicotinic acetyicholine receptors (or nAChRs). Nicotinic acetyicholine receptors are neuron receptor proteins which respond to the neurotransmitter acetylcholine.
In vitro: DHβE has been shown to be a purely competitive antagonist of the neuronal nicotinic receptor [1].
In vivo: DHβE is able to block some of the central actions of nicotine after systemic and intrathecal administration. The mechanism of blockade is different from that of mecamylamine, a classical ganglionic antagonist, and may involve a direct action of DHβE on nicotine receptor [2].
Clinical trial: DHβE can be given orally and may cross the blood-brain barriers. At 200 mg/kg, the effects were bradycardia and visual difficulty most often described as blurring of vision or double vision; at 6 mg/kg, produced aforementioned effects plus hypotension and reduction in grip strength with accompanying feelings of sedation [3].
References:
[1] Harvey SC, Maddox FN, Luetje CW. Multiple determinants of dihydro-beta-erythroidine sensitivity on rat neuronal nicotinic receptor alpha subunits. J Neurochem. 1996 Nov;67(5):1953-9.
[2] Damaj MI, Welch SP, Martin BR. In vivo pharmacological effects of dihydro-beta-erythroidine, a nicotinic antagonist, in mice. Psychopharmacology (Berl). 1995 Jan;117(1):67-73.
[3] MURPHREE HB. Effects in human volunteers of subparalytic doses of dihydro-beta-erythroidine. Clin Pharmacol Ther. 1963 May-Jun;4:304-10.
