Posted by Quintal on August 4, 2007, at 16:27:01
In reply to Re: Serotonin and Norepheniphrine together? » Quintal, posted by Klavot on August 4, 2007, at 7:09:57
Hello Klavot,
German chamomile contains volatile oils (alpha-bisabolol is the main one) that have anti-spasmodic and anti-inflammatory action, which can give relief from the nervous tension and stomach cramps associated with anxiety. Some also have mild sedative and anxiolytic properties. Being a natural plant product chamomile contains many substances, such as flavonoids, bitter glycosides and coumarin that contribute in synergy to the overall effect, which will be different from that of any one in isolation. Nevertheless, there is plenty of evidence to support the psychoactive properties of flavinoids contained in chamomile. Although their exact mode of action is unknown, this makes for an interesting branch of research in psychopharmacology, and may possibly lead to the discovery of new target mechanisms for synthetic pharmaceuticals.
__________________________________________________1: Fitoterapia. 2000 Aug;71 Suppl 1:S117-23.Click here to read Links
Behavioral characterisation of the flavonoids apigenin and chrysin.
Zanoli P, Avallone R, Baraldi M.Department of Pharmaceutical Sciences, Modena and Reggio Emilia University, Modena, Italy. zanoli.paola@unimo.it
The behavioral effects of acute administration of two flavonoids, apigenin and chrysin, contained in Matricaria chamomilla and in Passiflora incarnata, respectively, were studied in rats. The data demonstrate that in our experimental conditions, the two flavonoids were equally able to reduce locomotor activity when injected in rats at a minimal effective dose of 25 mg/kg. However, while chrysin exhibited a clear anxiolytic effect when injected at the dose of 1 mg/kg, apigenin failed to exert this activity. The sedative effect of these flavonoids cannot be ascribed to an interaction with GABA-benzodiazepine receptors, since it was not counteracted by the benzodiazepine antagonist Flumazenil. To the contrary, the anxiolytic effect of chrysin, which was blocked by the injection of Flumazenil, could be linked to an activation of the GABA(A) receptor unit.
PMID: 10930722 [PubMed - indexed for MEDLINE]
--------------------------------------------------2: Biochem Pharmacol. 2000 Jun 1;59(11):1387-94.Click here to read Links
Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla.
Avallone R, Zanoli P, Puia G, Kleinschnitz M, Schreier P, Baraldi M.Department of Pharmaceutical Sciences, Chair of Pharmacology and Pharmacognosy, Modena and Reggio Emilia University, 41100, Modena, Italy.
Dried flowers of Matricaria chamomilla L. are largely used to provide sedative as well as spasmolytic effects. In the present study, we examined in particular the pharmacological property of a fraction isolated from a methanolic extract of M. chamomilla, which was identified by HPLC-MS-MS analysis as apigenin. By radioreceptor binding assays, we demonstrated the ability of the flavone to displace a specific radioligand, [(3)H]Ro 15-1788, from the central benzodiazepine binding site. Electrophysiological studies performed on cultured cerebellar granule cells showed that apigenin reduced GABA (gamma-aminobutyric acid)-activated Cl(-) currents in a dose-dependent fashion. The effect was blocked by co-application of Ro 15-1788, a specific benzodiazepine receptor antagonist. Accordingly, apigenin reduced the latency in the onset of picrotoxin-induced convulsions. Moreover, apigenin injected i.p. in rats reduced locomotor activity, but did not demonstrate anxiolytic, myorelaxant, or anticonvulsant activities. The present results seem to suggest that the inhibitory activity of apigenin on locomotor behaviour in rats cannot be ascribed to an interaction with GABA(A)-benzodiazepine receptor but to other neurotransmission systems, since it is not blocked by Ro 15-1788.
PMID: 10751547 [PubMed - indexed for MEDLINE]
--------------------------------------------------3: Planta Med. 1995 Jun;61(3):213-6.Links
Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects.
Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC.Instituto de Biología Celular, Facultad de Medicina, Buenos Aires, Argentina.
The dried flower heads of Matricaria recutita L. (Asteraceae) are used in folk medicine to prepare a spasmolytic and sedative tea. Our fractionation of the aqueous extract of this plant led to the detection of several fractions with significant affinity for the central benzodiazepine receptor and to the isolation and identification of 5,7,4'-trihydroxyflavone (apigenin) in one of them. Apigenin competitively inhibited the binding of flunitrazepam with a Ki of 4 microM and had no effect on muscarinic receptors, alpha 1-adrenoceptors, and on the binding of muscimol to GABAA receptors. Apigenin had a clear anxiolytic activity in mice in the elevated plusmaze without evidencing sedation or muscle relaxant effects at doses similar to those used for classical benzodiazepines and no anticonvulsant action was detected. However, a 10-fold increase in dosage produced a mild sedative effect since a 26% reduction in ambulatory locomotor activity and a 35% decrement in hole-board parameters were evident. The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.
PMID: 7617761 [PubMed - indexed for MEDLINE]
--------------------------------------------------4: Pharmacol Biochem Behav. 1997 Dec;58(4):887-91.Click here to read Links
Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats.
Salgueiro JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I, Medina JH.Centro de Memoria, Departamento de Bioquímica, I.C.B.S., Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The naturally occurring flavonoids, chrysin (5,7-dihydroxyflavone) and apigenin (5,7,4'-trihydroxyflavone), and the synthetic compound, 6,3'-dinitroflavone have been recently reported to selectively bind with high affinity to the central benzodiazepine receptor, and to exert powerful anxiolytic and other benzodiazepine-like effects in rats. Their chemical analog, quercetin, shares none of these effects. In the present article we find that, in contrast to diazepam, chrysin, apigenin, and 6,3'-dinitroflavone have no amnestic effect on acquisition or retention of three different learning tasks (inhibitory avoidance, shuttle avoidance, and habituation to an open field), even when given at doses higher than those previously reported to be anxiolytic. Apigenin had a slight enhancing effect on training session performance and, when given posttraining, on test session retention, of crossing responses in the open field and hindered retention of inhibitory avoidance, and showed no anxiolytic action in an elevated plus maze. Unlike diazepam, none of these drugs had any analgesic effect in the tail-flick test. The data suggest that chrysin, apigenin, and 6,3'-dinitroflavoine, three flavonoids derivatives possessing anxioselective effects acting on central benzodiazepine receptors, may deserve clinical trials as anxiolytic agents.
PMID: 9408191 [PubMed - indexed for MEDLINE]
--------------------------------------------------5: Pharmacol Biochem Behav. 1994 Jan;47(1):1-4.Click here to read Links
Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea.
Wolfman C, Viola H, Paladini A, Dajas F, Medina JH.Instituto de Biología Celular, Facultad de Medicina, UBA, Argentina.
The pharmacological effects of 5,7-dihydroxyflavone (chrysin), a naturally occurring monoflavonoid that displaces [3H]flunitrazepam binding to the central benzodiazepine (BDZ) receptors, were examined in mice. In the elevated plus-maze test of anxiety, diazepam (DZ, 0.3-0.6 mg/kg) or chrysin (1 mg/kg) induced increases in the number of entries into the open arms and in the time spent on the open arms, consistent with an anxiolytic action of both compounds. The effects of chrysin on the elevated plus-maze was abolished by pretreatment with the specific BDZ receptor antagonist Ro 15-1788 (3 mg/kg). In the holeboard, diazepam (1 mg/kg) and chrysin (3 mg/kg) increased the time spent head-dipping. In contrast, high doses of DZ (6 mg/kg) but not of chrysin produced a decrease in the number of head dips and in the time spent head-dipping. In the horizontal wire test, diazepam (6 mg/kg) had a myorelaxant action. In contrast, chrysin (0.6-30 mg/kg) produced no effects in this test. These data suggest that chrysin possesses anxiolytic actions without inducing sedation and muscle relaxation. We postulate that this natural monoflavonoid is a partial agonist of the central BDZ receptors.
PMID: 7906886 [PubMed - indexed for MEDLINE]
__________________________________________________Synthetic flavonoids such as 6,3'-dinitroflavone have already been manufactured that are more potent than diazepam, cause less sedation, and have fewer adverse effects on learning and memory.
__________________________________________________1: J Pharm Pharmacol. 1999 May;51(5):519-26.Click here to read Links
Flavonoids and the central nervous system: from forgotten factors to potent anxiolytic compounds.
Paladini AC, Marder M, Viola H, Wolfman C, Wasowski C, Medina JH.Instituto de Quimica y Fisicoquimica Biologicas, Facultad de Farmacia y Bioquimica, Buenos Aires, Argentina.
The list of activities of plant flavonoids did not include effects on the central nervous system (CNS) up to 1990, when our laboratory described the existence of natural anxiolytic flavonoids. The first of these was chrysin (5,7-dihydroxyflavone), followed by apigenin (5,7,4'-trihydroxyflavone) and flavone itself. Semisynthetic derivatives of flavone obtained by introducing halogens, nitro groups or both in its molecule, give rise to high affinity ligands for the benzodiazepine receptor, active in-vivo; 6,3'-dinitroflavone, for example, is an anxiolytic drug 30 times more potent than diazepam. The data collected in this paper make clear that some natural flavonoids are CNS-active molecules and that the chemical modification of the flavone nucleus dramatically increases their anxiolytic potency.
PMID: 10411210 [PubMed - indexed for MEDLINE]
--------------------------------------------------2: Pharmacol Biochem Behav. 1997 Dec;58(4):887-91.Click here to read Links
Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats.
Salgueiro JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I, Medina JH.Centro de Memoria, Departamento de Bioquímica, I.C.B.S., Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The naturally occurring flavonoids, chrysin (5,7-dihydroxyflavone) and apigenin (5,7,4'-trihydroxyflavone), and the synthetic compound, 6,3'-dinitroflavone have been recently reported to selectively bind with high affinity to the central benzodiazepine receptor, and to exert powerful anxiolytic and other benzodiazepine-like effects in rats. Their chemical analog, quercetin, shares none of these effects. In the present article we find that, in contrast to diazepam, chrysin, apigenin, and 6,3'-dinitroflavone have no amnestic effect on acquisition or retention of three different learning tasks (inhibitory avoidance, shuttle avoidance, and habituation to an open field), even when given at doses higher than those previously reported to be anxiolytic. Apigenin had a slight enhancing effect on training session performance and, when given posttraining, on test session retention, of crossing responses in the open field and hindered retention of inhibitory avoidance, and showed no anxiolytic action in an elevated plus maze. Unlike diazepam, none of these drugs had any analgesic effect in the tail-flick test. The data suggest that chrysin, apigenin, and 6,3'-dinitroflavoine, three flavonoids derivatives possessing anxioselective effects acting on central benzodiazepine receptors, may deserve clinical trials as anxiolytic agents.
PMID: 9408191 [PubMed - indexed for MEDLINE]
--------------------------------------------------3: Neurochem Res. 1997 Apr;22(4):419-25.Links
Overview--flavonoids: a new family of benzodiazepine receptor ligands.
Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D, Paladini AC.Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, UBA, Paraguay, Buenos Aires, Argentina.
Benzodiazepines (BDZs) are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side-effects that they produce such as sedation, myorelaxation, ataxia, amnesia, ethanol and barbiturate potentiation and tolerance. Searching for safer BDZ-receptor (BDZ-R) ligands we have recently demonstrated the existence of a new family of ligands which have a flavonoid structure. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have shown to possess a selective and relatively mild affinity for BDZ-Rs and a pharmacological profile compatible with a partial agonistic action. In a logical extension of this discovery various synthetic derivatives of those compounds, such as 6,3'-dinitroflavone were found to have a very potent anxiolytic effect not associated with myorelaxant, amnestic or sedative actions. This dinitro compound, in particular, exhibits a high affinity for the BDZ-Rs (Ki = 12-30 nM). Due to their selective pharmacological profile and low intrinsic efficacy at the BDZ-Rs, flavonoid derivatives, such as those described, could represent an improved therapeutic tool in the treatment of anxiety. In addition, several flavone derivatives may provide important leads for the development of potent and selective BDZ-Rs ligands.
PMID: 9130252 [PubMed - indexed for MEDLINE]
--------------------------------------------------4: Eur J Pharmacol. 1996 Dec 27;318(1):23-30.Click here to read Links
Anxioselective properties of 6,3'-dinitroflavone, a high-affinity benzodiazepine receptor ligand.
Wolfman C, Viola H, Marder M, Wasowski C, Ardenghi P, Izquierdo I, Paladini AC, Medina JH.Instituo de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
6,3'-Dintroflavone is a synthetic flavone derivative with high affinity for central benzodiazepine receptors that has anxiolytic effects. Here, we describe its biochemical and pharmacological characterization. 6,3'-Dinitroflavone inhibited differentially [3H]flunitrazepam binding to central benzodiazepine receptors in several brain regions, showing a lower Ki value in the cerebellum (central benzodiazepine receptor type I-enriched area), and a higher Ki value in the spinal cord and in the dentate gyrus (central benzodiazepine receptor type II-enriched area). When i.p. injected in mice, 6,3'-dinitroflavone had a potent anxiolytic effect in the elevated plus maze test. This effect was blocked by the specific central benzodiazepine receptor antagonist, Ro 15-1788. 6,3'-Dinitroflavone did not exhibit anticonvulsant or myorelaxant effects in mice or amnestic effects in rats. Moreover, it abolished the myorelaxant effect of diazepam. On the other hand, 6,3'-dinitroflavone possessed a mild sedative action only at doses 100-300-fold greater than the anxiolytic one. Based on these findings, we suggest that 6,3'-dinitroflavone has a benzodiazepine partial agonist profile, with low selectivity for central benzodiazepine receptor types I and II.
PMID: 9007508 [PubMed - indexed for MEDLINE]
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poster:Quintal
thread:773847
URL: http://www.dr-bob.org/babble/20070730/msgs/773976.html