Efficacy of Hypnosis and Catalepsy Induction in Functional Neurological Disorders.

BACKGROUND: Patients with Functional Neurological Disorder (FND) experience complex patterns of motor and/or sensory symptoms. Treatment studies of psychological interventions are promising but limited. OBJECTIVES: The aim of the current pilot study is to investigate the effect of treatment consisting of a combination of hypnosis and catalepsy induction on FND symptom severity. METHODS: A within-subject waiting list-control design was used with 46 patients diagnosed with FND. The treatment consisted of 10 sessions. The primary outcome measure was FND symptom severity (The Psychogenic Movement Disorder Rating Scale; PMDRS). The secondary outcome measures were psychological distress and quality of life. RESULTS: The repeated measures (RM) ANOVA for the PMDRS as outcome measure revealed a significant effect for time with a large effect size (η2 = 0.679). Pairwise comparisons indicated that the effect of time in the treatment period was significant for the measure of FND symptom severity, whereas the waiting list period was not. The effect remained stable even at 8 weeks post treatment. As for the additional measurement, general psychological distress and quality of life, no statistically significant differences between individual time points were found. CONCLUSIONS: This pilot study showed that eight sessions of treatment consisting of a combination of hypnosis and catalepsy induction was effective in reducing FND symptom severity. Some explanations and limitations are provided in the paper as well as several avenues of future research.

4-Methoxycinnamic acid attenuates schizophrenia-like behaviors induced by MK-801 in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophularia buergeriana has been used for traditional medicine as an agent for reducing heat in the blood and for nourishing kidney 'Yin'. Therefore, S. buergeriana might be a potential treatment for mental illness, especially schizophrenia, which may be attenuated by supplying kidney Yin and reducing blood heat. In a pilot study, we found that S. buergeriana alleviated sensorimotor gating dysfunction induced by MK-801. AIM OF THE STUDY: In the present study, we attempted to reveal the active component(s) of S. buergeriana as a candidate for treating sensorimotor gating dysfunction, and we identified 4-methoxycinnamic acid. We explored whether 4-methoxycinnamic acid could affect schizophrenia-like behaviors induced by hypofunction of the glutamatergic neurotransmitter system. MATERIALS AND METHODS: Mice were treated with 4-methoxycinnamic acid (3, 10, or 30 mg/kg, i.g.) under MK-801-induced schizophrenia-like conditions. The effect of 4-methoxycinnamic acid on schizophrenia-like behaviors were explored using several behavioral tasks. We also used Western blotting to investigate which signaling pathway(s) is involved in the pharmacological activities of 4-methoxycinnamic acid. RESULTS: 4-Methoxycinnamic acid ameliorated MK-801-induced prepulse inhibition deficits, social interaction disorders and cognitive impairment by regulating the phosphorylation levels of PI3K, Akt and GSK-3ß signaling in the prefrontal cortex. And there were no adverse effects in terms of catalepsy and motor coordination impairments. CONCLUSION: Collectively, 4-methoxycinnamic acid would be a potential candidate for treating schizophrenia with fewer adverse effects, especially the negative symptoms and cognitive dysfunctions.

Pentadecapeptide BPC 157 counteracts L-NAME-induced catalepsy. BPC 157, L-NAME, L-arginine, NO-relation, in the suited rat acute and chronic models resembling 'positive-like' symptoms of schizophrenia.

In the suited rat-models, we focused on the stable pentadecapeptide BPC 157, L-NAME, NOS-inhibitor, and L-arginine, NOS-substrate, relation, the effect on schizophrenia-like symptoms. Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), BPC 157 (0.01), given alone and/or together, at 5 min before the challenge for the acutely disturbed motor activity (dopamine-indirect/direct agonists (amphetamine (3.0), apomorphine (2.5)), NMDA-receptor non-competitive antagonist (MK-801 (0.2)), or catalepsy, (dopamine-receptor antagonist haloperidol (2.0)). Alternatively, BPC 157 10 µg/kg was given immediately after L-NAME 40 mg/kg intraperitoneally. To induce or prevent sensitization, we used chronic methamphetamine administration, alternating 3 days during the first 3 weeks, and challenge after next 4 weeks, and described medication (L-NAME, L-arginine, BPC 157) at 5 min before the methamphetamine at the second and third week. Given alone, BPC 157 or L-arginine counteracted the amphetamine-, apomorphine-, and MK-801-induced effect, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization. L-NAME did not affect the apomorphine-, and MK-801-induced effects, haloperidol-induced catalepsy and chronic methamphetamine-induced sensitization, but counteracted the acute amphetamine-induced effect. In combinations (L-NAME + L-arginine), as NO-specific counteraction, L-NAME counteracts L-arginine-induced counteractions in the apomorphine-, MK-801-, haloperidol- and methamphetamine-rats, but not in amphetamine-rats. Unlike L-arginine, BPC 157 maintains its counteracting effect in the presence of the NOS-blockade (L-NAME + BPC 157) or NO-system-over-stimulation (L-arginine + BPC 157). Illustrating the BPC 157-L-arginine relationships, BPC 157 restored the antagonization (L-NAME + L-arginine + BPC 157) when it had been abolished by the co-administration of L-NAME with L-arginine (L-NAME + L-arginine). Finally, BPC 157 directly inhibits the L-NAME high dose-induced catalepsy. Further studies would determine precise BPC 157/dopamine/glutamate/NO-system relationships and clinical application.

Effect of M. chamomilla L. tea on chlorpromazine induced catalepsy: A neuroprotective study.

We determined anti-Parkinson's activity of M. chamomilla L. tea in chlorpromazine (CPZ) developed investigational animal model. In this research, effects of M. chamomilla L. tea 2.14ml/ kg P.O were studied on cataleptic behavior and its effect on brain histopathological changes and immunohistochemistry (IHC) in rats. The experimental design was developed by administering CPZ (3mg/kg, I/P) for twenty-one days to produce Parkinson's disease-like symptoms to 4 animal groups. We observed that chlorpromazine significantly produced motor dysfunctions (catalepsy) in a time period of twenty-one days. The M. chamomilla L. significantly (P<0.005) minimized/shorten/taper down catalepsy in rats just like standard group (Levodopa/carbidopa treated group). The maximum reduction was observed from both treated and standard groups on the 21st day. M. chamomilla L. treated rats mid brain sections showed presence of proliferative blood vessels, increase cellularity with reactive glial cells as compared to CPZ group. Furthermore, immunostaining CD68 & CD21 of M. chamomilla L. treated rats mid brain region showed few CD68 cells & no polymorphs neutrophils after CD21 staining. Thus, this research work disclosed the neuroprotective effect of M. chamomilla L. tea against Parkinson's disease-like symptoms or anti-Parkinson's activity induced by CPZ.

Modeling of Focal Seizures with Automatisms in Rats with Pendulum Movements.

Phenotypical study was carried out in rats with pendulum movements. The animals exhibited a high level of abortive seizures in response to audiogenic stimuli and longer postictal catalepsy in comparison with those in Wistar population. Seizure severity positively correlated with the duration of poststimulus catalepsy (r=0.90). High aggressiveness towards humans, the absence of BP elevation in stress, lower body weights, and lower weights of the kidneys and spleen in PM rats are considered concomitant traits. Correlations were detected between startle-1 and BP in rats with pendulum movements (r=0.70) and between startle-10 and BP in narcotized Wistar rats (r=-0.0.71). The newly described signs in rats with pendulum movements did not contradict the signs of the focal seizure model with typical automatisms in humans.

Coumarin analogue 3-methyl-7H-furo[3,2-g] chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

INTRODUCTION: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. OBJECTIVE: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. MATERIALS AND METHODS: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. RESULTS: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. CONCLUSION: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Role of Aqueous Extract of the Wood Ear Mushroom, Auricularia polytricha (Agaricomycetes), in Avoidance of Haloperidol-lnduced Catalepsy via Oxidative Stress in Rats.

Haloperidol-induced catalepsy is an animal model of a psychotic disorder that may be associated with neurodegeneration and free radical damage. Auricularia polytricha is effective in both prevention and treatment of numerous types of neurological disorders. In the present study, anticataleptic activity of aqueous extract of A polytricha (AEAP) at different doses (400 and 600 mg/kg, respectively, p.o.) was studied using haloperidol-induced (1 mg/ kg, i.p.) catalepsy in rats. Repeated treatment with haloperidol (1 mg/kg, i.p.) on each other day for 15 days (days 5, 10, and 15) significantly induced catalepsy in rats. The effect of AEAP at different doses (400 and 600 mg/kg, p.o.) on levels of superoxide dismutase, catalase, and glutathione reductase as well as inhibition of lipid peroxidation in the forebrain region was assessed. After 15 days of treatment, AEAP (400 and 600 mg/kg) significantly inhibited haloperidol-induced catalepsy. Treatment with AEAP (400 and 600 mg/kg) exhibited significant elevation in the levels of superoxide dismutase, catalase, and glutathione reductase as well as lipid peroxidation in the forebrain region compared to the haloperidol-treated group. The study concludes that AEAP (400 and 600 mg/kg) significantly protects animals against haloperidol-induced catalepsy.

Attenuation of brain mitochondria oxidative damage by Albizia julibrissin Durazz: neuroprotective and antiemetic effects.

Medicinal plants, as new drugs, are considered for treatment of insomnia, anxiety, depression, confusion, nausea, and vomiting symptoms. The current study aimed to evaluate the neuroprotective and antiemetic effects of Albizia. julibrissin Durazz. flower extract in the chickens. Emesis was induced by copper sulfate and ipecac (60 and 600 mg/kg, orally, respectively) and the methanolic extract (50, 100, and 200 mg/kg) were injected intraperitoneally (i.p.). Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC) content, and catalase activity as biomarkers of oxidative damage were evaluated in the brain mitochondria. All doses of extract showed significant (p < 0.001) antiemetic activity against induced emesis by copper sulfate and ipecac. Brain mitochondria function (by 50, 100, and 200 mg/kg of extract) were increased 48%, 85%, and 90% against emesis induced by ipecac and 32%, 18%, and 24% against emesis induced by copper sulfate, respectively. LPO and PC contents were significantly decreased after the administration of extract in emesis induced by copper sulfate and ipecac. A significant decrease (p < 0.01) of CAT activity was observed in the extract (200 mg/kg) group in emesis induced by copper sulfate in chickens brain mitochondria. The present study suggests that the extract had antiemetic effects against emesis induced by copper sulfate and ipecac in young chickens via peripheral and central mechanisms. Neuroprotective effect of the extract could be due to the increase in bioactive compounds, plasma antioxidants, or direct free radical scavenging that could prevent lipid and protein alteration and impede the formation of oxidative damage.

Antiasthmatic potential of Zizyphus jujuba Mill and Jujuboside B. - Possible role in the treatment of asthma.

Zizyphus jujuba Mill, a famous oriental traditional medicine, has been reported to exhibit diverse activities in biological systems including the respiratory system. However, a little information is available on its antiasthmatic activity. Jujuboside B (JB) is a natural saponin and one of the active constituent of fruits of Zizyphus jujuba. In the present investigation, JB was isolated from ethanolic extracts of fruits of Zizyphus jujuba (EZJF). EZJF and JB were then evaluated for anti-asthmatic activity using various screening methods. JB was additionally evaluated using ovalbumin (OVA) -induced allergic asthma in mice. Results obtained in the present study showed that EZJF and JB significantly inhibited clonidine-induced catalepsy, milk-induced leucocytosis and eosinophilia, clonidine-induced mast cell degranulation, and passive paw anaphylaxis. The number of inflammatory cells in bronchoalveolar lavage (BAL) fluid was considerably lowered and the severity of pulmonary inflammation was alleviated in the mice pretreated with JB. The high-level expression of T-helper type 2 (TH2) cytokines was markedly reduced in the serum, BAL fluid, and lung homogenates. Thus EZJF and JB showed potent anti-asthmatic activity. Hence EZJF and JB possess a potential role in the treatment of asthma.

Albizia zygia root extract exhibits antipsychotic-like properties in murine models of schizophrenia.

BACKGROUND: The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae) is used to manage mental disorders in African traditional medicine. However, its value, particularly, against negative and cognitive symptoms of schizophrenia have not been evaluated. AIM: The aim of this study was to evaluate the antipsychotic properties of the hydroethanolic root extract of Albizia zygia (AZE) against positive, negative and cognitive symptoms of schizophrenia in animal models. MATERIALS AND METHODS: The effects of AZE (30-300 mg kg-1) were evaluated against apomorphine-induced cage climbing as well as ketamine -induced hyperlocomotion, -enhanced immobility, -impaired social interaction and novel object recognition. The propensity of AZE to induce catalepsy and to attenuate haloperidol-induced catalepsy were also investigated. RESULTS: AZE 30-300 mg kg-1 significantly reduced apomorphine-induced climbing behaviour as well as ketamine-induced hyperlocomotion, immobility and object recognition deficits (at least P < 0.05). Moreover, the extract showed no cataleptic effect but significantly inhibited haloperidol-induced catalepsy at a dose of 30 mg kg-1 (P < 0.05). CONCLUSION: The root extract of Albizia zygia exhibited an antipsychotic-like activity in mice with potential to alleviate positive, negative and cognitive symptoms of schizophrenia.

Pharmacological interaction of Galphimia glauca extract and natural galphimines with Ketamine and Haloperidol on different behavioral tests.

Due to the high prevalence of psychiatric disorders and the prevalent side effects produced by the antipsychotic drugs available, it is necessary to search for new therapeutic options. Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases. From this plant, some compounds, denominated galphimines, have been discovered and have shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area. The objective of the present work was to evaluate the effect produced by the G. glauca extract, a Galphimine rich fraction (GRF), as well as the pure galphimines (G-A, G-B, and G-E) on behavioral models in mice. Products obtained from G. glauca were evaluated in the Haloperidol-induced catalepsy test and in the acute schizophrenia-like symptoms-induced with Ketamine (KET) in mice. Catalepsy was evaluated through the bar test, and schizophrenia-like symptoms, by means of the Open Field Test (OFT), Passive Avoidance Test (PAT), and the Forced Swimming Test (FST). The methanolic extract from G. glauca, GRF, and the pure galphimines were able to interact with the dopaminergic pathway and modify the behavioral response such as to potentiate the cataleptic effect induced with Haloperidol and to inhibit the behavior induced by KET in mice exposed to OFT, and FST. Moreover, the G. glauca extract and GRF were capable of blocking the cognitive decline that was induced with KET in mice (evaluated by PAT). Based on these results, it is possible to assume that part of the effect of G. glauca is due to the interaction of Galphimines with the dopaminergic and glutamatergic systems in vivo. It can be concluded that the products obtained from G. glauca potentiate the cataleptic effect induced with Haloperidol and show a protector effect on some of the symptoms generated by KET in mice (KET is capable of provoking halucinations in humans and psychosis-like behaviour in mice). With this basis, the metanolic extract from G. glauca, and the GRF are capable of blocking positive and cognitive symptoms associated with psychosis induced by KET. In addition, it could be suggested that the galphimines are responsible for the inhibition of the positive symptoms observed.

Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine.

Parkinson's disease (PD) is a neurodegenerative disease characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc), with consequent depletion of dopamine in the striatum, which gives rise to the characteristic motor symptoms of PD. Although its etiology is unknown, several studies have suggested that oxidative stress plays a critical function in the pathophysiology of PD, and antioxidant agents could be helpful to slown down the dopaminergic neurodegeneration. Carvacrol (CA) is a phenolic monoterpene found in essential oils of many aromatic plants that presents antioxidant and neuroprotective effects. This study aimed to assess the effect of CA in a reserpine (RES)-induced rat model of PD. Male Wistar rats received 15 s.c. injections of 0.1 mg/kg RES or vehicle, every other day, concomitantly to daily i.p. injections of CA (12.5 or 25 mg/kg) or vehicle. Across the treatment, the animals were submitted to behavioral evaluation in the catalepsy test (performed daily), open field test (7th day) and assessment of vacuous chewing movements (12th, 20th and 30th days). Upon completion of behavioral tests, rats were perfused and their brains underwent tyrosine hydroxylase (TH) immunohistochemical analysis. Our results showed that CA (12.5 e 25 mg/kg) prevented the increase in catalepsy behavior and number of vacuous chewing movements, but failed to revert the decreased open-field locomotor activity induced by RES. In addition, CA in both doses prevented the decrease in TH immunostaining induced by RES in the SNpc and dorsal striatum. Taken together, our results suggest that CA shows a protective effect in a rat model of PD, preventing motor and neurochemical impairments induced by RES. Thus, the use of CA as a promising new strategy for the prevention and/or treatment of PD may be considered.

Antiallergic and antihistaminic actions of Ceasalpinia bonducella seeds: Possible role in treatment of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Seed kernel of the plant Ceasalpinia bonducella Linn (Caesalpiniacaeae) are used for the treatment of asthma in folk medicine and ancient books. AIM OF STUDY: To assess the pharmacological efficacy of the plant in asthma and to confine and describe the synthetic constituents from the seeds that are in charge of the action. MATERIAL AND METHODS: The viability of petroleum ether, ethanol extract and ethyl acetate fraction from ethanol extract of C. bonducella seeds were screened for the treatment of asthma by various methods viz. effect of test drug on clonidine and haloperidol induced catalepsy, milk-induced leukocytosis and eosinophilia, mast cell stabilizing activity in mice and studies on smooth muscle preparation of guinea pig ileum (in-vitro). Column chromatography of active extract was done to pinpoint the active compound followed by structure elucidation by FTIR, GCMS and NMR spectroscopic methods. RESULTS: Ethyl acetate fraction from ethanol extract of C. bonducella seeds exhibited antihistaminic activity at the dose of 50 and 100 mg/kg, inhibited clonidine-induced catalepsy but not haloperidol-induced catalepsy. Ethyl acetate fraction from ethanol extract significantly inhibited increased leukocyte and eosinophil count due to milk allergen and showed maximum protection against mast cell degranulation by clonidine. The results of guinea pig ileum indicated that the compound 2 methyl, 1 hexadecanol isolated from ethyl acetate fraction of ethanol extract relaxed significantly the ileum muscle strips pre-contracted by which suggests the involvement of ß2-agonists on the relaxation of the tissue. All the results are dose dependent. Active ethyl acetate fraction from ethanol extract showed presence of anti-asthmatic compound, 2-methyl, 1-hexadecanol. CONCLUSION: The ethyl acetate fraction from ethanol extract of seeds of the plant C. bonducella can inhibit parameters linked to asthma disease.

Extract of Synedrella nodiflora (L) Gaertn exhibits antipsychotic properties in murine models of psychosis.

BACKGROUND: The hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) has demonstrated anticonvulsant, sedative and analgesic effects. Preliminary studies conducted in animals, SNE significantly decreased stereotypic behaviours suggesting antipsychotic potential. Coupled with the central nervous system depressant effects of SNE, we hypothesized that it may have utility in the management of psychosis. The present study therefore investigated the antipsychotic potential of the SNE in several murine models of psychosis. METHOD: The primary central nervous system activities of SNE (30-3000 mg/kg, p.o) were investigated using the Irwin's test. The novelty-induced rearing, locomotion and stereotypy counts provoked by SNE (100-1000 mg/kg, p.o) were conducted using the open-field paradigm. The antipsychotic test models used in the screening of SNE (100-1000 mg/kg, p.o) included apomorphine-induced stereotypy, rearing, locomotion and cage climbing activities. The combined effects of a low dose of SNE (100 mg/kg) with various doses of haloperidol and chlorpromazine were analysed using the apomorphine-induced cage climbing and stereotypy, respectively. The ability of SNE to cause catalepsy in naïve mice as well as its effect on haloperidol-induced catalepsy was assessed. RESULTS: SNE showed acetylcholine-like and serotonin-like activities in the Irwin test, with sedation occurring at high doses. SNE significantly reduced the frequencies of novelty- and apomorphine-induced rearing and locomotion; stereotypy behaviour and the frequency and duration of apomorphine-induced cage climbing in mice. In all the tests performed, SNE was less potent than the reference drugs used (chlorpromazine and haloperidol). In addition, SNE potentiated the effects of haloperidol and chlorpromazine on apomorphine-induced cage climbing and stereotypy activities in mice. CONCLUSION: SNE, while exhibiting antipsychotic properties itself, can also potentiate the antipsychotic effects of chlorpromazine and haloperidol.

An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice.

BACKGROUND: Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. METHODS: The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. RESULTS: The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin's test. No lethality was observed after 24 h post-treatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. CONCLUSIONS: The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.

Discovery of Novel and Selective Adenosine A2A Receptor Antagonists for Treating Parkinson's Disease through Comparative Structure-Based Virtual Screening.

Among non-dopaminergic strategies for combating Parkinson's disease (PD), antagonism of the A2A adenosine receptor (AR) has emerged to show great potential. In this study, on the basis of two crystal structures of the A2A AR with the best capability to distinguish known antagonists from decoys, docking-based virtual screening (VS) was conducted to identify novel A2A AR antagonists. A total of 63 structurally diverse compounds identified by VS were submitted to experimental testing, and 11 of them exhibited substantial activity against the A2A AR (Ki < 10 µM), including two compounds with Ki below 1 µM (compound 43, 0.42 µM; compound 51, 0.27 µM) and good A2A/A1 selectivity (fold < 0.1). Compounds 43 and 51 demonstrated antagonistic activity according to the results of cAMP measurements (cAMP IC50 = 1.67 and 1.80 µM, respectively) and showed good efficacy in the haloperidol-induced catalepsy (HIC) rat model for PD at doses of up to 30 mg/kg. Further lead optimization based on a substructure searching strategy led to the discovery of compound 84 as an excellent A2A AR antagonist (A2A Ki = 54 nM, A2A/A1 fold < 0.1, cAMP IC50 = 0.3 µM) that exhibited significant improvement in anti-PD efficacy in the HIC rat model.

5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice.

All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests that additional drug targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss-promoting capabilities. A difficulty in developing 5-HT2C agonists is that most ligands also possess 5-HT2B and/or 5-HT2A activities. We have developed selective 5-HT2C ligands and herein describe their preclinical effectiveness for treating schizophrenia-like behaviors. JJ-3-45, JJ-3-42, and JJ-5-34 reduced amphetamine-stimulated hyperlocomotion, restored amphetamine-disrupted prepulse inhibition, improved social behavior, and novel object recognition memory in NMDA receptor hypofunctioning NR1-knockdown mice, and were essentially devoid of catalepsy. However, they decreased motivation in a breakpoint assay and did not promote reversal learning in MK-801-treated mice. Somewhat similar effects were observed with lorcaserin, a 5-HT2C agonist with potent 5-HT2B and 5-HT2A agonist activities, which is approved for treating obesity. Microdialysis studies revealed that both JJ-3-42 and lorcaserin reduced dopamine efflux in the infralimbic cortex, while only JJ-3-42 decreased it in striatum. Collectively, these results provide additional evidence that 5-HT2C receptors are suitable drug targets with fewer side effects, greater therapeutic selectivity, and enhanced efficacy for treating schizophrenia and related disorders than current APDs.

Anti-Psychotic Activity of Aqueous Root Extract of Hemidesmus indicus: A Time Bound Study in Rats.

AIMS AND BACKGROUND: Psychosis is a neurological disorder, which is usually defined as the &quot;loss of contact with reality.&quot; As medicine 'Hemidesmusindicus' holds a reputed place in all systems of medicine in India. It is given in the form of infusion, fine particles, or syrup. It is also a component of several medicinal preparations. The present research work is pertaining to find out an anti-psychotic activity of an aqueous root extract of Hemidesmusindicus- a time bound study in rats. METHODS: In the present study, the dried roots of Hemidesmusindicus were crushed to a coarse powder and extracted with water under reflux for 36 hours to obtain the aqueous extract of roots of Hemidesmusindicus (AERHI). The extract was reconstituted in 2% aqueous tragacanth just before use and administered orally at a dose 0f 100 mg/kg, 300 mg/kg and 500 mg/kg. In a single dose study, the parameters were assessed after oral administration of the single dose of the AERHI, whereas in a multiple dose study, the animals daily received the suitable oral dose of the AERHI for a period of 30 days. The parameters were assessed on the 15th and 30th day. The antipsychotic activity was screened using Apomorphine induced Stereotyped behavior in rats and Haloperidol induced catalepsy models were used. In Apomorphine induced Stereotyped behavior inhibition of the Stereotyped behavior was considered to be anti-psychotic activity and in Haloperidol induced catalepsy, we observed whether the AERHI potentate or attenuate the catalepsy in rats. RESULTS: In this study, the extract of Hemidesmusindicus significantly inhibited the stereotyped behavior induced by apomorphine in rats and also potentiate the catalepsy induced by haloperidol, thereby showing its anti-psychotic activity. CONCLUSION: All these observations imply that Hemidesmusindicus extract possesses anti-psychotic activity in experimental animals.

Influence of magnesium supplementation on movement side effects related to typical antipsychotic treatment in rats.

Chronic use of typical antipsychotic haloperidolis related to movement disturbances such as parkinsonism, akathisia and tardive dyskinesia which have been related to excitotoxicity in extrapyramidal brain areas, requiring their prevention and treatment. In the current study we evaluated the influence of the magnesium on prevention (for 28days before-), reversion (for 12days after-) and concomitant supplementation on haloperidol-induced movement disorders in rats. Sub-chronic haloperidol was related to orofacial dyskinesia (OD) and catalepsy development, increased generation of reactive species (RS) and levels of protein carbonyl (PC) in cortex, striatum and substantia nigra (SN) in all experimental protocols. When provided preventatively, Mg reduced the increase of OD and catalepsy time 14 and 7days after haloperidol administration, respectively. When supplemented after haloperidol-induced OD establishment, Mg reversed this behavior after 12days, while catalepsy was reversed after 6days of Mg supplementation.When Mg was concomitantly supplemented with haloperidol administration, OD and catalepsy were prevented. Moreover, Mg supplementation was able to prevent the RS generation in both cortex and SN, reducing PC levels in all brain areas evaluated. When supplemented after haloperidol, Mg reversed RS generation in cortex and striatum, decreasing PC levels in SN and striatum.The co-administration of haloperidol and Mg supplementation prevented RS generation in cortex, striatum and SN, and PC levels in the SN.These outcomes indicate that Mg supplementation may be a useful alternative to prevent movement disturbances resulting of classic antipsychotic pharmacotherapy as haloperidol.