Sorption of Neuropsychopharmaca in Microfluidic Materials for In Vitro Studies.

Sorption (i.e., adsorption and absorption) of small-molecule compounds to polydimethylsiloxane (PDMS) is a widely acknowledged phenomenon. However, studies to date have largely been conducted under atypical conditions for microfluidic applications (lack of perfusion, lack of biological fluids, etc.), especially considering biological studies such as organs-on-chips where small-molecule sorption poses the largest concern. Here, we present an in-depth study of small-molecule sorption under relevant conditions for microphysiological systems, focusing on a standard geometry for biological barrier studies that find application in pharmacokinetics. We specifically assess the sorption of a broad compound panel including 15 neuropsychopharmaca at in vivo concentration levels. We consider devices constructed from PDMS as well as two material alternatives (off-stoichiometry thiol-ene-epoxy, or tape/polycarbonate laminates). Moreover, we study the much neglected impact of peristaltic pump tubing, an essential component of the recirculating systems required to achieve in vivo-like perfusion shear stresses. We find that the choice of the device material does not have a significant impact on the sorption behavior in our barrier-on-chip-type system. Our PDMS observations in particular suggest that excessive compound sorption observed in prior studies is not sufficiently described by compound hydrophobicity or other suggested predictors. Critically, we show that sorption by peristaltic tubing, including the commonly utilized PharMed BPT, dominates over device sorption even on an area-normalized basis, let alone at the typically much larger tubing surface areas. Our findings highlight the importance of validating compound dosages in organ-on-chip studies, as well as the need for considering tubing materials with equal or higher care than device materials.

Characteristic Volatile Composition of Seven Seaweeds from the Yellow Sea of China.

Plant volatile organic compounds (VOCs) represent a relatively wide class of secondary metabolites. The VOC profiles of seven seaweeds (Grateloupia filicina, Polysiphonia senticulosa, Callithamnion corymbosum, Sargassum thunbergii, Dictyota dichotoma, Enteromorpha prolifera and Ulva lactuca) from the Yellow Sea of China were investigated using multifiber headspace solid phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS), among them, the VOCs of three red algae Grateloupia filicina, Polysiphonia senticulosa, and Callithamnion corymbosum were first reported. Principal component analysis (PCA) was used to disclose characteristic categories and molecules of VOCs and network pharmacology was performed to predict potential biomedical utilization of candidate seaweeds. Aldehyde was found to be the most abundant VOC category in the present study and (E)-ß-ionone was the only compound found to exist in all seven seaweeds. The chemical diversity of aldehydes in E. prolifera suggest its potential application in chemotaxonomy and hinted that divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber is more suitable for aldehyde extraction. VOCs in D. dichotoma were characterized as sesquiterpenes and diterpenes and the most relevant pharmacological pathway was the neuroactive ligand-receptor interaction pathway, which suggests that D. dichotoma may have certain preventive and therapeutic values in cancer, especially in lung cancer, in addition to neuropsychiatric diseases.

NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases.

NRF2 acts by controlling gene expression, being the master regulator of the Phase II antioxidant response, and also being key to the control of neuroinflammation. NRF2 activity is regulated at several levels, including protein degradation by the proteasome, transcription, and post-transcription. The purpose of this review is to offer a concise and critical overview of the main mechanisms of NRF2 regulation and their actual or potential use as targets for the treatment of neurodegenerative diseases.

Uncaria rhynchophylla and its Major Constituents on Central Nervous System: A Review on Their Pharmacological Actions.

BACKGROUND: Uncaria rhynchophylla (Miq.) Jacks (Rubinaceae), a common herbal medicine known as Gou-teng in Chinese, is commonly used in Chinese medicine practice for the treatment of convulsions, hypertension, epilepsy, eclampsia and other cerebral diseases. The major active components of U. rhynchophylla are alkaloids, terpenoids and flavonoids. The protective effects of U. rhynchophylla and its major components on central nervous system (CNS) have become a focus of research in recent decades. OBJECTIVE: The study aimed to systematically summarize the pharmacological activities of U. rhynchophylla and its major components on the CNS. METHODS: This review summarized the experimental findings from our laboratories, together with other literature data obtained through a comprehensive search of databases including the Pubmed and the Web of Science. RESULTS: U. rhynchophylla and its major components such as rhynchophylline and isorhynchophylline have been shown to have neuroprotective effects on Alzheimer's disease, Parkinson's disease, depression, cerebral ischaemia through a number of mechanisms including anti-oxidant, anti-inflammatory actions and regulation on neurotransmitters. CONCLUSION: U. rhynchophylla and its major components have multiple beneficial pharmacological effects on CNS. Further studies on U. rhynchophylla and its major components are warranted to fully illustrate the underlying molecular mechanisms, pharmacokinetics, and toxicological profiles of these naturally occurring compounds and their potential for clinical application.

Role of piperine in CNS diseases: pharmacodynamics, pharmacokinetics and drug interactions.

Introduction: Piperine, the major bioactive component from black pepper, has gained increasing attention for its beneficial effects in the central nervous system (CNS). However, its related pharmacodynamics and brain pharmacokinetics, as well as its interaction with other CNS drugs are lacking, which may hinder its therapeutic and safe use. Areas covered: The current review provides an updated summary on CNS activities of piperine, including anti-epileptic, anti-depressive and neurodegeneration protection effect. The brain pharmacokinetic properties of piperine together with the approaches to enhance its aqueous solubility were summarized. Considering the wide use of black pepper and the well-reported alteration on CYP and transporters by piperine, interactions between piperine and CNS drugs are also illustrated for the first time. Expert opinion: Although the CNS beneficial effects of piperine have been extensively studied in preclinical models, clinical evidence on its CNS application is barely available, which may be attributed to its limited aqueous solubility, unclear pharmacokinetic properties in humans and potential toxicities during long-term use at higher doses. Although beneficial interactions between piperine and certain CNS drugs were often reported in preclinical studies, more mechanistic studies with clinically relevant doses should be conducted to provide guidance on their clinical combination use.

New Depsides and Neuroactive Phenolic Glucosides from the Flower Buds of Rugosa Rose ( Rosa rugosa).

The flower buds of Rosa rugosa Thunb. have been commonly used as a source of rose oil and as an ingredient in tea in eastern Asia, including China, Japan, and Korea. Repeated chromatography of a hot water extract from the flower buds of R. rugosa led to the isolation and characterization of three new depside glucosides, rosarugosides A-C (1-3), along with three phenolic compounds, one ionone glucoside, four flavonoids, and two tannins having known chemical structures. Linarionoside A and 2-phenylethyl-(6- O-galloyl)-ß-d-glucopyranoside were isolated from R. rugosa for the first time in this study. The structures of the new compounds 1-3 were elucidated by interpreting one- and two-dimensional nuclear magnetic resonance spectroscopic and mass spectrometric data. Among the isolates, a new depside glucoside (1) and two major phenolic glucosides (4 and 5) improved MK-801-induced sensorimotor gating deficits, which were measured via an acoustic startle response test in mice.

Comparison of neuropharmacological activities of methanolic extracts of Cuminum nigrum (Linn.) and Centratherum anthelminticum (Linn.) in mice.

The study is conducted to observe and investigate the effects of oral dosing of methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) on neuropharmacological activities of mice. Methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) were soluble in Dimethyl sulphoxide (DMSO) i.e. an organic solvent, so it is used in this study. Screening for anxiolytic and antidepressant effects were performed using open field test, head dip test, stationary rod test, cage crossing test, light and dark box and swimming- induced depression test. Thirty animals were divided into three groups of 10 animals each and numbered as 1 (control, on DMSO), 2(on methanolic extract of Cuminum nigrum (L), 3 (on methanolic extract of Centratherum anthelminticum (L). The extracts and DMSO were administered orally for 60 days. Any possible change in animal behavior was evaluated on day 15, 30 and 60 of dosing. The groups 2 and 3 showed significant increase (p<0.001, p<0.01) in open field activity and light and dark box test respectively, while significantly decreased activity was observed in head dip and cage crossing activity (p<0.01) after 60 days of dosing. Based on above findings, it is suggested that the extracts of Centratherum anthelminticum (L) and Cuminum nigrum (L) have antidepressant and anxiolytic potential with sedative effects.

Extracellular Application of CRMP2 Increases Cytoplasmic Calcium through NMDA Receptors.

Collapsin Response Mediator Protein 2 (CRMP2) is an intracellular protein involved in axon and dendrite growth and specification. In this study, CRMP2 was identified in a conditioned media derived from degenerated sciatic nerves (CM). On cultured rat hippocampal neurons, acute extracellular application of CM or partially purified recombinant CRMP2 produced an increase in cytoplasmic calcium. The increase in cytoplasmic calcium was mostly mediated through NMDA receptors, with a minor contribution of N-type VDCC, and it was maintained as long as CM was present. By using live-labeling of CRMP2, Ca2+ channel binding domain 3 (CBD3) peptide derived from CRMP2, and recombinant CRMP2, we demonstrated that that this effect was mediated by an action on the extracellular side of the NMDA receptor. This is the first report of an extracellular action of CRMP2. Prolonged exposure to extracellular CRMP2, may contribute to neuronal calcium dysregulation and neuronal damage.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling.

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

ISOLATION OF NOVEL PARA-PENTYL PHENYL BENZOATE FROM MONDIA WHITEI. (HOOK.F.) SKEELS (PERIPLOCACEAE), ITS STRUCTURE, SYNTHESIS AND NEUROPHARMACOLOGICAL EVALUATION.

BACKGROUND: Mondia whitei L. (Hook. F.) Skeels (Periplocaceae) is a medicinal plant used locally in managing pain, fever, loss of appetite and as aphrodiasc in the South-Western states of Nigeria. However, the fruit is consumed habitually in the South-Eastern states of Nigeria, leading to speculation that it may possess some central nervous system effect but which has not been scientifically investigated, hence this study. METHODOLOGY: Fresh fruits of Mondia whitei were collected and identified by a taxonomist. They were chopped into small pieces and extracted with absolute ethanol. The crude extract was subjected to various chromatographic techniques to isolate a novel compound whose structure was elucidated from the analysis of the crystal data and by extensive use of spectroscopy. The structure was confirmed by synthesis. The compound was subjected to anxiolytic and sedative activity assay. Computational analysis of the receptor binding event of isolated compound at the gamma amino butyric acid A receptor was also evaluated. RESULTS: The structure of the compound was elucidated as para pentyl phenyl benzoate. The neuropharmacological evaluation of the compound indicated significant (p<0.05) depression of the central nervous system. The binding characteristics of the compound to gamma amino butyric acid A receptors appears to be more favorable than those obtained for gamma amino butyric acid, chlorpromazine, benzamidine, and is comparable with the affinity obtained for pentobarbitone and diazepam. CONCLUSION: These present data provide evidence for the role of para pentyl phenyl benzoate in the habitual consumption of the fruit as well as its central nervous system activities.

Chemical Composition and in Vitro Antimicrobial, Cytotoxic, and Central Nervous System Activities of the Essential Oils of Citrus medica L. cv. 'Liscia' and C. medica cv. 'Rugosa' Cultivated in Southern Italy.

Citrus medica cv. 'liscia' and C. medica cv. 'rugosa' are two taxa of citron, belonging to the biodiversity of South Italy, in particular of Amalfi Coast, in the Campania region. The chemical composition of the essential oils (EOs) from fruit peels of both C. medica cultivars was studied by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses. In all, 100 compounds were identified, 82 for C. medica cv. 'liscia', accounting for 91.4% of the total oil, and 88 for C. medica cv. 'rugosa', accounting for 92.0% of the total oil. Monoterpene hydrocarbons are the main constituents in both oils of C. medica cv. 'liscia' (79.1%) and C. medica cv. 'rugosa' (80.2%). In both oils, limonene (67.2%-62.8%) and camphene (8.5%-10.9%) are the main constituents. The antimicrobial activity of the EOs was assayed against some bacterial strains: Bacillus cereus (DSM 4313), Bacillus cereus (DSM 4384), Staphylococcus aureus (DSM 25693), Pseudomonas aeruginosa (ATCC 50071), and Escherichia coli (DSM 8579). Low concentrations of C. medica cv. 'rugosa' EO showed an inhibitory effect on P. aeruginosa and higher concentrations inhibited more B. cereus (4384) and E. coli than S. aureus. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line. The influence of the EO on the expression of adenylate cyclase 1 (ADCY1) was also studied. The antimicrobial activity registered confirm their traditional uses as food preserving agents and led us to hypothesize the possible use of these oils as antimicrobials. The alterations in ADCY1 expression suggested a role for limonene in effects on the central nervous system.

Occurrence and fate of amisulpride, sulpiride, and lamotrigine in municipal wastewater treatment plants with biological treatment and ozonation.

This study examines the transformation and removal of the atypical antipsychotics amisulpride and sulpiride and the anticonvulsant lamotrigine in municipal wastewater treatment plants (WWTPs). Amisulpride, sulpiride and lamotrigine were selected using a tailored non-target screening approach. In WWTPs, lamotrigine concentrations increased from 1.1 to 1.6µg/L while sulpiride and amisulpride exhibited similar concentrations, up to 1.1µg/L and 1.3µg/L, respectively. It was found that N2-glucuronide conjugates of lamotrigine were cleaved to form lamotrigine. Both lamotrigine and amisulpride were detected in groundwater with a concentration of 0.07µg/L. Sulpiride was identified but not quantified. This demonstrates that amisulpride, sulpiride and lamotrigine might be used as indicators for treated wastewater in raw waters used for drinking water production. Furthermore, it could be shown that all three pharmaceutical compounds are efficiently oxidized by ozonation, leading mainly to N-oxide oxidation products. No significant removal of the N-oxides of amisulpride, sulpiride and lamotrigine was observed in the bench-scale biodegradation experiments with activated sludge. This indicated their high biological persistence. Therefore, N-oxides might be appropriate as indicators for post-ozonation as a major technology for the advanced treatment of secondary effluent.

Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities.

Annona muricata is a member of the Annonaceae family and is a fruit tree with a long history of traditional use. A. muricata, also known as soursop, graviola and guanabana, is an evergreen plant that is mostly distributed in tropical and subtropical regions of the world. The fruits of A. muricata are extensively used to prepare syrups, candies, beverages, ice creams and shakes. A wide array of ethnomedicinal activities is contributed to different parts of A. muricata, and indigenous communities in Africa and South America extensively use this plant in their folk medicine. Numerous investigations have substantiated these activities, including anticancer, anticonvulsant, anti-arthritic, antiparasitic, antimalarial, hepatoprotective and antidiabetic activities. Phytochemical studies reveal that annonaceous acetogenins are the major constituents of A. muricata. More than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots and fruits of A. muricata. In view of the immense studies on A. muricata, this review strives to unite available information regarding its phytochemistry, traditional uses and biological activities.

Identification and analysis of gastrodin and its five metabolites using ultra fast liquid chromatography electrospray ionization tandem mass spectrometry to investigate influence of multiple-dose and food.

A reliable and highly sensitive ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) analytical method was developed for identification and quantification of gastrodin (GAS) and its metabolites in rat plasma. Five metabolites were identified: p-formylphenyl-ß-d-glucopyranoside (M1), p-hydroxybenzonic acid (M2), p-hydroxybenzyl alcohol (M3), p-formaldehydephenyl-ß-d-glucopyranoside (M4), p-hydroxybenzaldehyde (M5). The molecular structures of metabolites were proposed based on the characters of their precursor ions, product ions and chromatographic retention time. Four of them were reported firstly in rat plasma. This method involved the addition of bergeninum as the internal standard (IS), UFLC separation, and quantification by MS/MS system using negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The lower limit of quantification of gastrodin and five metabolites were all 1ng/mL. The method was linear in the concentration range of 0.001-10µg/mL. The intra- and inter-day precisions (R.S.D %) were within 15.0% for all analytes. No interference was noted due to endogenous substances. All analytes were stable in rat plasma stored at room temperature and 4°C for at least 4h, -20°C combined with three freeze-thaw cycles for at least 1 month. By this method, the influence of multiple-dose and food on the pharmacokinetics behaviors of GAS and its metabolites were studied for the first time. We hope pharmacokinetic data of present study may inspire rational clinical usage of GAS.

Neuropharmacological screening of essential oil from oleo gum resin of Gardenia lucida Roxb.

ETHNOPHARMACOLOGICAL RELEVANCE: The oleo gum resin of Gardenia lucida is commonly employed in traditional medicine to treat multiple ailments, including epilepsy and mania. The essential oil isolated from it was screened for CNS activities to check if it is responsible for the claims made regarding the traditional use of the oleo gum resin. MATERIALS AND METHODS: The hypnotic and anticonvulsant activity was assessed by pentobarbitone induced hypnosis and convulsant models-Maximum electroshock (MES) and Pentylene tetrazole (PTZ) respectively. Effect on motor activity was evaluated using an actophotometer, rotarod and grip strength methods. RESULTS: The oil significantly potentiated the barbitone induced hypnosis and offered significant protection against the intensity and frequency of convulsions and mortality rate in both the convulsant models. A significant decrease in locomotion, motor impairment and loss of gripping reflex was also observed. CONCLUSION: The essential oil of the oleo gum resin of Gardenia lucida is a CNS depressant and anticonvulsant with central muscle relaxant properties. This justifies the claims made regarding the use of the oleo gum resin of Gardenia lucida in CNS disorders.

Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters.

Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations±standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700±1000 ng L(-1), 2100±1700 ng L(-1), carbamazepine and 10-hydroxy-carbamazepine 480±380 ng L(-1), 360±400 ng L(-1), venlafaxine and O-desmethyl-venlafaxine 1400±1300 ng L(-1), 1800±2300 ng L(-1). Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that this is likely a global environmental issue, and further understanding of the environmental fate and impacts of these compounds is warranted.

Molecularly imprinted-solid phase extraction combined with simultaneous derivatization and dispersive liquid-liquid microextraction for selective extraction and preconcentration of methamphetamine and ecstasy from urine samples followed by gas chromatography.

In this study, a developed technique was reported for extraction and pre-concentration of methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) from urine samples using molecularly imprinted-solid phase extraction (MISPE) along with simultaneous derivatization and dispersive liquid-liquid microextraction (DLLME). Molecularly imprinted microspheres as sorbent in solid phase extraction (SPE) procedure were synthesized using precipitation polymerization with MAMP as the template. Aqueous solution of the target analytes was passed through MAMP-MIP cartridge and the adsorbed analytes were then eluted with methanol. The collected eluate was mixed with butylchloroformate which served as the derivatization reagent as well as the extraction solvent. The mixture was immediately injected into deionized water. After centrifugation, 1 µL of the settled organic phase was injected into gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS). Various experimental parameters affecting the performance of both of the steps (MISPE and DLLME) were thoroughly investigated. The calibration graphs were linear in the ranges of 10-1500 ng mL(-1) (MAMP) and 50-1500 ng mL(-1) (MDMA), and the detection limits (LODs) were 2 and 18 ng mL(-1), respectively. The relative standard deviations (%RSDs) obtained for six repeated experiments (100 ng mL(-1) of each drug) were 5.1% and 6.8% for MAMP and MDMA, respectively. The relative recoveries obtained for the analytes in human urine samples, spiked with different levels of each drug, were within the range of 80-88%.

Preclinical evaluation of Trichilia catigua extracts on the central nervous system of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichilia catigua preparations have been popularly used in Brazil as a tonic for the treatment of fatigue, stress, impotence, and deficiency of memory. The aim of the present study was to investigate the possible antidepressant, anxiolytic, motor and cognitive effects of the crude extract (CE) or ethyl-acetate fraction (EAF) of Trichilia catigua. Analyses of the total phenolics and total tannins content, as well as the in vitro antioxidant activity of CE and EAF were also performed. MATERIALS AND METHODS: CE (200-800 mg/kg) and EAF (100-400mg/kg) were orally administered to mice and 1h later the behavioral tests were performed. The free radical scavenging activity was measured by using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) method. RESULTS: Single administration of CE (200-400 mg/kg) or EAF (100-400 mg/kg) did not change the behavior of the animals submitted to the elevated plus maze or their locomotor activity in the open field test. An antidepressant-like effect was detected with EAF (400 mg/kg) after acute administration. Both CE (800 mg/kg) and EAF (200 and 400 mg/kg), improve memory in mice as measured by an increased latency in the step-down inhibitory avoidance test. The EAF presented higher total phenolics and total tannins as compared to CE as well as it exhibited the best antioxidant activity. CONCLUSIONS: The present results showed an in vitro antioxidant activity for EAF and suggested that it may be useful for cognitive improvement. It is possible that both functional and chemical activities are related.

Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats.

AIM OF THE STUDY: Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats. MATERIALS AND METHODS: 4-5 weeks Spraque-Dawley rats were administered with concentration 1, 3, 5, 10, 30 mg/kg of A-A, baclofen, scopolamine and saline intra peritoneally and were evaluated for passive avoidance (PA), active avoidance (AA) and changes in blood pressure (BP). RESULTS: Treatment 30 mg/kg of A-A resulted in significantly dose-dependently improved memory, with increased retention latency to enter difference compartment in PA test compared to baclofen, saline and scopolamine. Furthermore, 30 mg/kg of A-A was significantly higher on learning abilities on 1st day but there was no significantly difference on avoidance memory ability after 7 days of retention. Low reading in blood pressure dose-dependent significantly difference was observed in the 30 mg/kg of A-A group compared to saline group. CONCLUSIONS: Administration A-A facilitated PA and AA on memory and learning and but had no effect on active avoidance on memory. Hence, may serve useful memory and learning with less effect in blood pressure in promoting memory and learning increases.