Abin-Carriquiry_2006_Eur.J.Pharmacol_536_1

Reference

Title : C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists - Abin-Carriquiry_2006_Eur.J.Pharmacol_536_1
Author(s) : Abin-Carriquiry JA , Voutilainen MH , Barik J , Cassels BK , Iturriaga-Vasquez P , Bermudez I , Durand C , Dajas F , Wonnacott S
Ref : European Journal of Pharmacology , 536 :1 , 2006
Abstract :

Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, found in Leguminosae spp., binds with high affinity to alpha4beta2* nicotinic receptors. We have compared the effect of C3 and C5 halogenation of cytisine and methylcytisine (MCy) on their interaction with native rat nicotinic receptors. 3-Bromocytisine (3-BrCy) and 3-iodocytisine (3-ICy) exhibited increased binding affinity (especially at alpha7 nicotinic receptors; Ki approximately 0.1 microM) and functional potency, whereas C5-halogenation was detrimental. 3-BrCy and 3-ICy were more potent than cytisine at evoking [3H]dopamine release from striatal slices (EC50 approximately 11 nM), [3H]noradrenaline release from hippocampal slices (EC50 approximately 250 nM), increases in intracellular Ca2+ in PC12 cells and inward currents in Xenopus oocytes expressing human alpha3beta4 nicotinic receptor (EC50 approximately 2 microM). These compounds were also more efficacious than cytisine. C3-halogenation of cytisine is proposed to stabilize the open conformation of the nicotinic receptor but does not enhance subtype selectivity.

PubMedSearch : Abin-Carriquiry_2006_Eur.J.Pharmacol_536_1
PubMedID: 16563372

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Citations formats

Abin-Carriquiry JA, Voutilainen MH, Barik J, Cassels BK, Iturriaga-Vasquez P, Bermudez I, Durand C, Dajas F, Wonnacott S (2006)
C3-halogenation of cytisine generates potent and efficacious nicotinic receptor agonists
European Journal of Pharmacology 536 :1

Abin-Carriquiry JA, Voutilainen MH, Barik J, Cassels BK, Iturriaga-Vasquez P, Bermudez I, Durand C, Dajas F, Wonnacott S (2006)
European Journal of Pharmacology 536 :1