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DOI: 10.1055/s-0030-1250406
© Georg Thieme Verlag KG Stuttgart · New York
Annomontine, an Alkaloid Isolated from Annona purpurea, Has Anxiolytic-Like Effects in the Elevated Plus-Maze
Publikationsverlauf
received June 26, 2010
revised Sept. 4, 2010
accepted Sept. 10, 2010
Publikationsdatum:
01. Oktober 2010 (online)
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Abstract
The effects of annomontine, a pyrimidine-β-carboline alkaloid isolated from the root of Annona purpurea, on anxiety was studied in mice using the elevated plus-maze. The behavioral effects of this alkaloid on the pentobarbital-induced hypnosis, the locomotor activity in an open field, and the motor coordination in the rotarod test were also evaluated. The intraperitoneal injection of annomontine (1–30 mg/kg) increased in a dose-dependent way the number of visits to and the time spent in the open arms of the elevated plus-maze in comparison to the control animals. Such effects were blocked by the prior application of flumazenil (3 mg/kg; i. p.), a specific antagonist for the binding of benzodiazepines on the GABAA receptor. Under the same experimental conditions annomontine failed to affect the behavior of the animals in the pentobarbital-induced hypnosis test and had no effects on locomotion and motor coordination. These results suggest that annomontine possesses anxiolytic-like effects which may be mediated at the level of the benzodiazepine binding site on the GABAA receptor.
Key words
Annona purpurea - Annonaceae - anxiety - anxiolytic - annomontine - GABAA‐benzodiazepine receptor
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References
- 1 Leboeuf M, Cavé A, Forgacs P, Provost J, Chiaroni A, Riche C. Alkaloids of the Annonaceae. Part 33. Annomontine and methoxyannomontine, two new pyrimidine-P carboline-type alkaloids from Annona montana. J Chem Soc [Perkin I]. 1982; 1205-1208
- 2 Costa E V, Pinheiro M L B, Xavier C M, Silva J R A, Amaral A C F, Souza A D L, Barison A, Campos F R, Ferreira A G, Machado G M C, Leon L L P. A pyrimidine-β-carboline and other alkaloids from Annona foetida with antileishmanial activity. J Nat Prod. 2006; 69 292-294
- 3 Costa E V, Pinheiro M L B, Souza A D L, Gama D A S, Ramos C F, Ferreira A G, Barison A. Full NMR analysis of annomontine, methoxyannomontine and N-hydroxyannomontine pyrimidine-β-carboline alkaloids. Magn Reson Chem. 2008; 46 69-74
- 4 Leboeuf M, Cavé A, Forgacs P, Tiberghien R, Provost J, Touche A, Jacquemin H. Alcaloïdes des annonacées XL+: Étude chimique et pharmacologique des alcaloïdes de l′ Annona montana MACF. Plantes Médicinales et Phytothérapie. 1982; 16 169-184
- 5 Husbands S M, Glennon R A, Gorgerat S, Gough R, Tyacke R, Crosby J, Nutt D J, Lewis J W, Hudson A L. β-carboline binding to imidazoline receptors. Drug Alcohol Depend. 2001; 64 203-208
- 6 Rommelspacher H, May T, Susilo R. β-Carbolines and tetrahydroisoquinolines: detection and function in mammals. Planta Med. 1991; 57 S85-S92
- 7 Glennon R A, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson M V. Binding of beta-carbolines and related agents at serotonin (5-HT[2] and 5-HT[1A]), dopamine (D[2]) and benzodiazepine receptors. Drug Alcohol Depend. 2000; 60 121-132
- 8 McCormick S J, Tunnicliff G. Inhibitors of synaptosomal γ-hydroxybutyrate transport. Pharmacology. 1998; 57 124-131
- 9 Anderson N J, Robinson E S J, Husbands S M, Delagrange P, Nutt D J, Hudson A L. Characterisation of [3H]harmane binding to rat whole brain membranes. Ann NY Acad Sci. 2003; 1009 175-179
- 10 Hilber P, Chapillon P. Effects of harmaline on anxiety-related behavior in mice. Physiol Behav. 2006; 86 164-167
- 11 Aricioglu F, Altunbas H. Harmane induces anxiolysis and antidepressant-like effects in rats. Ann NY Acad Sci. 2003; 1009 196-201
- 12 González-Esquinca A R. Contribución al estudio del género Annona (Annonaceae). Análisis filoquímico de tres especies del Estado de Chiapas. México; Universidad Nacional Autónoma de México 2001
- 13 Silvania M M, Macedo D S, Melo C T, Monteiro A P, Rodriguez A C. Central activity of hydroalcoholic extracts from Erythrina velutina and Erythrina mulungu in mice. J Pharm Pharmacol. 2004; 56 389-393
- 14 Lister R G. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology. 1987; 92 180-185
- 15 Pellow S, Chopin P, File S E, Briley M. Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985; 14 149-167
- 16 Treit D, Menard J, Royan C. Anxiogenic stimuli in the elevated plus-maze. Pharmacol Biochem Behav. 1993; 44 463-469
- 17 Archer J. Test for emotionality in rat and mice: a review. Anim Behav. 1973; 21 205-235
- 18 de Sousa D P, de Almeida R N. Neuroleptic-like properties of the chloroform extract of Maytenus obtusifolia Mart. roots. Biol Pharm Bull. 2005; 28 224-225
- 19 Sugimoto Y, Furutani S, Itoh A, Tanahashi T, Nakajima H, Oshiro H, Sun S, Yamada J. Effects of extracts and neferine from the embryo of Nelumbo nucifera seeds on the central nervous system. Phytomedicine. 2008; 15 1117-1124
- 20 González-Trujano M E, Navarrete A, Reyes B, Cedillo-Portugal E, Hong E. Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia. Planta Med. 2001; 67 136-141
- 21 Pérez de la Mora M, Lara García D, Jacobsen K X, Vázquez-García M, Crespo-Ramírez M, Flores-Gracia C, Escamilla-Marvan E, Fuxe K. Anxiolytic-like effects of the selective metabotropic glutamate receptor 5 antagonist MPEP after its intra-amygdaloid microinjection in three different non-conditioned rat models of anxiety. Eur J Neurosci. 2006; 23 2749-2759
- 22 Pérez de la Mora M, Hernández-Gómez A M, Arizmendi-García Y, Jacobsen K X, Lara García D, Flores-Gracia C, Crespo-Ramírez M, Gallegos-Cari A, Nuche-Bricaire A, Fuxe K. Role of the amygdaloid cholecystokinin (CCK)/gastrin-2 receptors and terminal networks in the modulation of anxiety in the rat. Effects of CCK-4 and CCK-8S on anxiety-like behavior and [3H]GABA release. Eur J Neurosci. 2007; 26 3614-3630
- 23 Pérez de la Mora M, Gallegos-Cari A, Arizmendi-García Y, Marcellino D, Fuxe K. Role of the dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: structural and functional analysis. Prog Neurobiol. 2010; 90 198-216
- 24 Henniger M S H, Ohl F, Hölter S M, Weißenbacher P, Toschi M, Lörscher P, Wigger A, Spangel R, Landgraf R. Unconditioned anxiety and social behavior in two rat lines selectively bred for high and low anxiety-related behavior. Behav Brain Res. 2000; 111 153-163
- 25 Goloubkova T D, Heckler E, Rates S M, Henriques J A, Henriques A T. Inhibition of cytochrome P450-dependent monooxygenases by an alkaloid fraction from Helietta apiculata markedly potentiates the hypnotic action of pentobarbital. J Ethnopharmacol. 1998; 60 141-148
- 26 Jakovljevic V, Raskovic A, Popovic M, Sabo J. The effect of celery and parsley juices on the pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism. Eur J Drug Metab Pharmacokinet. 2002; 27 153-156
- 27 Jakovljevic V, Raskovic A, Popovic M, Sabo J, Bursac M. The effect of methoxsalene of hypnotic and subhypnotic doses of pentobarbital. Eur J Drug Metab Pharmacokinet. 2002; 27 149-151
- 28 File S E, Lister R G, Nutt D J. The anxiogenic action of benzodiazepine antagonists. Neuropharmacology. 1982; 21 1033-1037
- 29 Frostholm A, Evans J E, Cummings S L, Rotter A. Harmaline-induced changes in gamma aminobutyric acidA receptor subunit mRNA expression in murine olivocerebellar nuclei. Brain Res Mol Brain Res. 2000; 85 200-208
- 30 Braestrup C, Nielsen M, Honore T, Jensen L H, Petersen E N. Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology. 1983; 22 1451-1457
- 31 Crawley J N, Ninan P T, Pickar D, Chrousos G P, Linnoila M, Skolnick P, Poul S M. Neuropharmacological antagonism of the β-carboline induced “anxiety” response in rhesus monkeys. J Neurosci. 1985; 5 477-485
Dr. José del Carmen Rejón-Orantes
Laboratorio Experimental de Farmacobiología
Facultad de Medicina, Universidad Autónoma de Chiapas
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C. P. 29040
México
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