Inhibition of [³ H]Citalopram Binding to the Rat Brain Serotonin Transporter by Amaryllidaceae Alkaloids

Abstract

Twenty-one Amaryllidaceae alkaloids isolated from different Amaryllidaceae species were investigated for their affinity to the serotonin reuptake transport protein and for GABA_A-benzodiazepine receptor binding. Cherylline (21), crinamine (7), crinine (1), epibuphanisine (2), epivittatine (6), maritidine (11), O-methylmaritidine (12), powelline (3), 1-O-acetyllycorine (18) and tazettine (13) showed affinity to the serotonin reuptake transport protein. Cherylline (21) and epivittatine (6) yielded the highest activity among the group. No GABA_A-benzodiazepine receptor binding activity was exhibited by the alkaloids tested.

References

• 1 Pollock B G. Citalopram: a comprehensive review.  Exp Opin Pharmacother. 2001;  2 681-98
• 2 Holden C. Global survey examines impact of depression.  Science. 2000;  288 39-40
• 3 Davidson C, Stanford J A. The effect of paroxetine on 5-HT efflux in the rat dorsal raphe nucleus is potentiated by both 5HT1A and 5-HT1B/D receptor antagonists.  Neurosci Lett. 1995;  188 41-4
• 4 Witchel H J, Pabbathi V K, Hofmann G, Paul A A, Hancox J C. Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents.  FEBS Lett. 2002;  512 59-66
• 5 Neckelmann D, Bjorvatn B, Bjørkum A A, Ursin R. Citalopram: different sleep/wake and EEG power spectrum effects after single dose and chronic administration.  Behav Brain Res. 1996;  79 183-92
• 6 Kahnberg P, Lager E, Rosenberg C, Schougaard J, Camet L, Sterner O. et al . Refinement and evaluation of a pharmacophore model for flavone derivatives binding to the benzodiazepine site of the GABA_A receptor.  J Med Chem. 2002;  45 4188-201
• 7 Chattopadhyah S, Chattopadhyah U, Marhur P P, Saini K S, Ghosal S. Effects of hippadine, an Amaryllidaceae alkaloid, on testicular function in rats.  Planta Med. 1983;  49 252-4
• 8 Ghosal S, Saini K S, Razdan S. Crinum alkaloids: their chemistry and biology.  Phytochemistry. 1985;  24 2141-56
• 9 Spoeroke D G, Smolinske S C. Toxicity of houseplants. Boca Raton; CRS Press 1990
• 10 Harborne J B, Baxter H. Phytochemical dictionary: a handbook of bioactive compounds from plants. London; Taylor & Francis 1993
• 11 Lewis J R. Amaryllidaceae alkaloids.  Nat Prod Rep. 1990;  9 183-91
• 12 Elgorashi E E, Stafford G I, van Staden J. Acetylcholinestrase enzyme inhibitory effects of Amaryllidaceae alkaloids.  Planta Med. 2004;  70 260-2
• 13 Sandager M, Nielsen N D, Stafford G I, van Staden J, Jäger A K. Alkaloids from Boophane disticha with affinity to the serotonin transporter in rat brain.  J Ethnopharmacol. 2005;  98 367-70
• 14 Elgorashi E E, Drewes S E, van Staden J. Alkaloids from Crinum moorei .  Phytochemistry. 2001;  56 637-40
• 15 Elgorashi E E, Drewes S E, van Staden J. Alkaloids from Crinum bulbispermum .  Phytochemistry. 1999;  53 533-6
• 16 Elgorashi E E, Drewes S E, van Staden J. Alkaloids from Crinum macowanii .  Biochem Syst Ecol. 2001;  29 749-50
• 17 Elgorashi E E, van Staden J. Alkaloids from Cyrtanthus falcatus .  S Afr J Bot. 2003;  69 593-4
• 18 Plenge P, Mellerup E T, Nielsen M. Inhibitory and regulatory binding sites on the rat brain serotonin transporter: molecular weight of the [³ H]citalopram binding proteins.  Eur J Pharmacol. 1990;  189 129-34
• 19 Nielsen N D, Sandager M, Stafford G I, van Staden J, Jager A K. Screening of indigenous plants from South Africa for affinity to the serotonin reuptake transport protein.  J Ethnopharmacol. 2004;  94 159-63
• 20 Risa J, Risa A, Adsersen A, Gauguin B, Stafford G I, van Staden J. et al . Screening of plants used in southern Africa for epilepsy and convulsions in the GABA_A-benzodiazepine receptor assay.  J Ethnopharmacol. 2003;  93 177-82