Design of selective TACE inhibitors using molecular docking studies: Synthesis and preliminary evaluation of anti-inflammatory and TACE inhibitory activity.

Tumor necrosis factor-α (TNF-α) converting enzyme (TACE) has been considered one of the principal therapeutic targets for the treatment of TNF-dependent pathologies. Several TACE inhibitors have been reported, but none of them has been successfully passed to phase II clinical trials. In the present work, we attempted to design highly selective new non-hydroxamate sulfonamide TACE inhibitors. The docking study was performed on one of the crystal structures of TACE, selected based on its resolution and R value, to tackle the flexibility issue of the active site. The results allowed us to distinguish the analogues with a higher binding affinity toward the active site of TACE and to identify the substituent of analogues needed for binding with the surrounding site of the enzyme. Finally the analogues were docked on crystal structures of six different matrix metalloproteinases (MMPs) for a selectivity study of TACE over MMPs. Some of these analogues were synthesized and subjected to preliminary testing for in vivo anti-inflammatory activity and TACE inhibitory activity.

Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy.

Oxidative stress is closely associated with the pathophysiology of diabetic cardiomyopathy (DCM). The mitochondrial flavoenzyme monoamine oxidase A (MAO-A) is an important source of oxidative stress in the myocardium. We sought to determine whether MAO-A plays a major role in modulating DCM. Diabetes was induced in Wistar rats by single intraperitoneal injection of streptozotocin (STZ). To investigate the role of MAO-A in the development of pathophysiological features of DCM, hyperglycemic and age-matched control rats were treated with or without the MAO-A-specific inhibitor clorgyline (CLG) at 1 mg/kg/day for 8 weeks. Diabetes upregulated MAO-A activity; elevated markers of oxidative stress such as cardiac lipid peroxidation, superoxide dismutase activity, and UCP3 protein expression; enhanced apoptotic cell death; and increased fibrosis. All these parameters were significantly attenuated by CLG treatment. In addition, treatment with CLG substantially prevented diabetes-induced cardiac contractile dysfunction as evidenced by decreased QRS, QT, and corrected QT intervals, measured by ECG, and LV systolic and LV end-diastolic pressure measured by microtip pressure transducer. These beneficial effects of CLG were seen despite the persistent hyperglycemic and hyperlipidemic environments in STZ-induced experimental diabetes. In summary, this study provides strong evidence that MAO-A is an important source of oxidative stress in the heart and that MAO-A-derived reactive oxygen species contribute to DCM.

Estimation of the Long-term Cardiovascular Events Using UKPDS Risk Engine in Metabolic Syndrome Patients.

Long-term cardiovascular complications in metabolic syndrome are a major cause of mortality and morbidity in India and forecasted estimates in this domain of research are scarcely reported in the literature. The aim of present investigation is to estimate the cardiovascular events associated with a representative Indian population of patients suffering from metabolic syndrome using United Kingdom Prospective Diabetes Study risk engine. Patient level data was collated from 567 patients suffering from metabolic syndrome through structured interviews and physician records regarding the input variables, which were entered into the United Kingdom Prospective Diabetes Study risk engine. The patients of metabolic syndrome were selected according to guidelines of National Cholesterol Education Program - Adult Treatment Panel III, modified National Cholesterol Education Program - Adult Treatment Panel III and International Diabetes Federation criteria. A projection for 10 simulated years was run on the engine and output was determined. The data for each patient was processed using the United Kingdom Prospective Diabetes Study risk engine to calculate an estimate of the forecasted value for the cardiovascular complications after a period of 10 years. The absolute risk (95% confidence interval) for coronary heart disease, fatal coronary heart disease, stroke and fatal stroke for 10 years was 3.79 (1.5-3.2), 9.6 (6.8-10.7), 7.91 (6.5-9.9) and 3.57 (2.3-4.5), respectively. The relative risk (95% confidence interval) for coronary heart disease, fatal coronary heart disease, stroke and fatal stroke was 17.8 (12.98-19.99), 7 (6.7-7.2), 5.9 (4.0-6.6) and 4.7 (3.2-5.7), respectively. Simulated projections of metabolic syndrome patients predict serious life-threatening cardiovascular consequences in the representative cohort of patients in western India.

Reduced ulcerogenic potential and antiarthritic effect of chitosan-naproxen sodium complexes.

The purpose of this research was to address the utility of naproxen sodium-chitosan spray-dried complexes for antiulcer and antiarthritic activities. The cold stress technique was used to examine the ulcerogenic potential of naproxen sodium (NPX) and spray-dried formulations in the different doses. The ulcerations reduced with the dose of spray-dried complexes of naproxen sodium and chitosan. The conspicuous hemorrhagic lesions were visible in the morphological features of the animal treated with naproxen 50 mg/kg (p.o.). Thus, the results suggest that the spray-dried naproxen sodium-chitosan complex (NPXF) was not corrosive to the gastric mucosa at high doses of 50, 100, and 200 mg/kg (p.o.) under stressful conditions. It is evident from the present investigation that NPXF does not possess any ulcerogenic potential in comparison to naproxen which, under stressful conditions, led to the hypersecretion of HCl, culminating to petichial hemorrhages in the gastric mucosa of the animals. The biphasic pattern was observed in the various arthritic parameters. The rise in paw volume, joint diameter, WBC count, arthritis score, and fall in body weight was significantly ameliorated in the animals treated with NPXF (5, 10, and 20 mg/kg, p.o). At the end of the study, slight erythema was visible in the naproxen-treated animals. However, no erythema, redness, or ulcers were visible in the animals treated with NPXF. Thus, the direct compression properties and reduced ulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability toward the drug, make naproxen sodium-chitosan spray-dried complexes particularly suitable for developing a reduced-dose, fast-release, solid oral dosage form of naproxen.

Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice.

OBJECTIVE: To investigate the anticonvulsant activity of the lobeline isolated from the Lobelia nicotianaefolia in chemoconvulsant-induced seizures and its biochemical mechanism by investigating relationship between seizure activities and altered gamma amino butyric acid (GABA) in brain of mice in Pentylenetetrazol (PTZ) seizure models. METHODS: The anticonvulsant activity of the isolated lobeline (5, 10, 20 and 30 mg/kg, i.p.) was investigated in PTZ and strychnine induced seizures in mice and the effect of isolated lobeline on brain GABA level in seizures induced by PTZ. Diazepam was used as reference anticonvulsant drugs for comparison. RESULTS: Isolated lobeline (10, 20 and 30 mg/kg, i.p.) significantly delayed and antagonized (P < 0.050-0.001) the onset of PTZ-induced seizures. It also antagonized strychnine induced seizures. The mortality was also prevented in the test group of animals. In biochemical evaluation, isolated lobeline (5, 10 and 20 mg/kg, i.p.) significantly increased the brain GABA level. And at dose of 30 mg/kg GABA level showed slight decrease in PTZ model. CONCLUSIONS: In our findings, isolated lobeline (20mg/kg) exhibited potent anticonvulsant activity against PTZ induced seizures. Also a biochemical evaluation suggested significant increase in barain GABA level at 20 mg/kg i.p. of isolated lobeline. Hence, we may propose that lobeline reduces epileptic seizures by enhancing the GABA release supporting the GABAergic mechanism.

Synthesis and neuromuscular blocking activity of 16-(2- and 3-pyridylmethylene) dehydroepiandrosterone derivatives.

The interonium distance plays a major role in neuromuscular blocking activity of bis-quaternary ammonium compounds. In this study we tried to alter the distance between two quaternary nitrogens in some of the steroidal derivatives synthesized and evaluated them for neuromuscular blocking activity using in vivo (in chicks) and in vitro models (rectus abdominus and chick biventer cervis muscle) for their mechanism of action. All the synthesized compounds have shown to possess good depolarizing, competitive neuromuscular blocking activity, particularly the 17-acetoxy derivative and the increase in the distance between two quaternary nitrogens decreased the activity.

Cardioprotective and ß-adrenoceptor antagonistic activity of a newly synthesized aryloxypropanolamine derivative PP-36.

The present study was performed to evaluate the cardioprotective effects and pharmacological characterization of newly synthesized ß-adrenoreceptor antagonists 3-(3-tert-butylamino-2-hydroxypropoxy)-4-methoxybenzaldehyde (PP-36) in the rat model of coronary artery occlusion and reperfusion. Pre-ischemic administration (20 minutes before coronary occlusion) of PP-36 showed cardioprotective effects against ischemia/reperfusion injury in rats. PP-36 (6 mg kg(-1)) significantly reduced arrhythmia score (6.33 ± 0.55, P < 0.05), infarct size/left ventricle size (38.9 ± 3.2, P < 0.05) and no mortality compared to vehicle-treated control group (14.17 ± 1.83, 44.9 ± 4.6 and 17% respectively). In-vitro studies in rat isolated right atria, guinea-pig trachea and rat distal colon preparations, were carried out to investigate the potency of PP-36 towards different ß-adrenoceptor subtypes. pA2/pKB values of PP-36 for ß1-ß2-and ß3-adrenoceptors were 6.904 ± 0.190, 6.44 ± 0.129 and 5.773 ± 0.129, respectively. In conclusion, PP-36 is a ß-adrenoceptor antagonist possessing potent anti-arrhythmic and cardioprotective effects against ischemia/reperfusion injury in rats.

Anticonvulsant Activity of Argyreia speciosa in Mice.

Argyreia speciosa commonly known as Vridha daraka in Sanskrit is one of the important plants used in indigenous system of medicine. The root is regarded as an alternative tonic and useful in the diseases of nervous system. To confirm the veracity of aforementioned claim, we have evaluated the anticonvulsant effect of the extract. In this investigation, the mice were pretreated with different doses of Argyreia speciosa extract (100, 200, 400 mg/kg) for 10 days and then, they were subjected to either pentylenetetrazole (80 mg/kg) or maximal electroshock seizures (50 mA, 0.2 s) treatment. The hydroalcoholic extract of Argyreia speciosa at the dose of 200 and 400 mg/kg significantly delayed the latency to the onset of first clonus as well as onset of death in unprotected mice and exhibited protection in 16.66% and 33.33% of pentylenetetrazole treated mice respectively. Whereas in case of maximal electroshock-seizures, the dose of 200 and 400 mg/kg significantly reduced the duration of hind limb extension and both the doses were statistically found to be equipotent. The reference standards, clonazepam (0.1 mg/kg) and phenytoin (20 mg/kg) provided complete protection. Thus, present study revealed anticonvulsant effect of Argyreia speciosa against pentylenetetrazole- and maximal electroshock-induced convulsions in mice.

Beta-blocking activity of PP-34, a newly synthesized aryloxypropanolamine derivative, and its cardioprotective effect against ischaemia/reperfusion injury in laboratory animals.

Beta-adrenoceptor antagonists are widely used in cardiovascular medicine. However, the main side effect of these drugs is due to antagonism of beta(2)-adrenoceptors in the airways, resulting in bronchospasm. Therefore, more cardioselective beta-blockers have been developed to offer a lower side effect profile. We have studied a new aryloxypropanolamine derivative (PP-34) with more cardioselectivity and efficacy against ischaemia/reperfusion injury in rats. Oxalate salts of 1-(tert-butylamino)-3-(5-tert-butylaminomethyl-2-methoxyphenoxy) propan-2-ol (PP-34) is a novel beta-adrenoceptor antagonist. In-vitro studies in rat isolated right atria, guinea-pig trachea and rat distal colon preparations were carried out to investigate the potency of PP-34 towards different beta-adrenoceptor subtypes. pA(2)/pK(B) values of PP-34 for beta(1), beta(2), and beta(3) adrenoceptor were 7.89+/-0.15, 6.13+/-0.09 and 6.30+/-0.19, respectively. The beta(1)/beta(2) selectivity ratio calculated was in the order of PP-34 > atenolol > propranolol. Pre-ischaemic administration (20 min before coronary occlusion) of PP-34 (0.3 or 1 mg kg(-1)) showed cardioprotective effects against ischaemia/reperfusion injury in rats and significantly reduced arrhythmias, infarct area and necrosis induced by ischaemia/reperfusion injury. The efficacy of PP-34 was found to be greater then atenolol. In conclusion, PP-34 is a cardioselective beta-adrenoceptor antagonist, possessing potent anti-arrhythmic and cardioprotective effects against ischaemia/reperfusion injury in rats.

Evaluation of anti-diarrhoeal property and acute toxicity of Triphala Mashi, an Ayurvedic formulation.

The anti-diarrhoeal effect of aqueous and alcoholic extracts of Triphala and Triphala Mashi were studied employing castor oil-induced-diarrhoeal model in rats. The gastrointestinal transit rate was expressed as the percentage of the longest distance travelled by the charcoal divided by the total length of the small intestine. All the extracts, at various doses 200, 400 and 800 mg/kg displayed remarkable anti-diarrhoeal activity as evidenced by a significant increase in first defecation time, cumulative fecal weight and intestinal transit time. Aqueous and alcoholic extracts of Triphala and Triphala Mashi were considered safe up to a dose of 1750 mg/kg when evaluated for acute oral toxicity in accordance with the OECD (Organization for Economic Cooperation and Development) guidelines. In conclusion, the remarkable anti-diarrhoeal effect of Triphala and Triphala Mashi extracts against castor oil-induced diarrhoea suggest its potential for application in a wide range of diarrhoeal states.

Parkinson's disease: genetics and beyond.

Parkinson's disease (PD) is characterized clinically by resting tremor, rigidity, bradykinesia and postural instability due to progressive and selective loss of dopamine neurons in the ventral substantia nigra, with the presence of ubiquitinated protein deposits called Lewy bodies in the neurons. The pathoetiology of cell death in PD is incompletely understood and evidence implicates impaired mitochondrial complex I function, altered intracellular redox state, activation of proapoptotic factors and dysfunction of ubiquitinproteasome pathway. Now it is believed that genetic aberration, an environmental toxin or combination of both leads to a cascade of events culminating in the destruction of myelinated brainstem catecholaminergic neurons. Also the role of production of significant levels of abnormal proteins, which may misfold, aggregate and interfere with intracellular processes causing cytotoxicity has recently been hypothesized. In this article, the diverse pieces of evidence that have linked the various factors responsible for the pathophysiology of PD are reviewed with special emphasis to various candidate genes and proteins. Furthermore, the present therapeutic strategies and futuristic approaches for the pharmacotherapy of PD are critically discussed.

Antipsychotic induced metabolic abnormalities: an interaction study with various PPAR modulators in mice.

Abnormalities in glucose and lipid regulation have been reported in schizophrenia during antipsychotic medications. The objectives of the present study were to evaluate the effect of various peroxisome proliferator-activated receptor modulators viz. glimepiride, rosiglitazone and fenofibrate on chlorpromazine, clozapine and ziprasidone induced hyperglycemia and hyperlipidemia in mice. Male Swiss albino mice were orally treated with chlorpromazine, clozapine and ziprasidone concurrently with the antidiabetic medications for 7 days. Plasma glucose, insulin and triglyceride levels were determined at the end of the study. Chlorpromazine and clozapine elevated the glucose and triglyceride levels in normal mice, with no effect on insulin but ziprasidone increased the basal triglyceride and insulin levels and did not have any effect on glucose. Glimepiride and rosiglitazone showed beneficial glucose and triglyceride lowering effects in chlorpromazine and clozapine animals and no effect on insulin levels. Fenofibrate significantly reduced the glucose levels only in animals treated with clozapine, and exhibited significant reduction of triglyceride levels in chlorpromazine, clozapine and ziprasidone treated animals. All three antidiabetic/hypolipidemic agents lowered triglyceride and insulin levels in ziprasidone treated animals. The results of the present studies suggest that hyperglycemia, hyperinsulinemia and hypertriglyceridemia induced by various antipsychotics may involve diverse mechanisms.

Migraine: current therapeutic targets and future avenues.

Migraine is characterized by attacks of intense pulsatile and throbbing headache, typically unilateral in nature with or without aura. Migraine affects a substantial fraction (10-20 %) of the world population (more women than men). With regard to the pathophysiology of migraine, several theories have been proposed; the major three are vascular (due to cerebral vasodilatation), neurological (abnormal neurological firing) and neurogenic dural inflammation (release of inflammatory neuropeptides). The drugs used to treat migraine can be divided into two groups: agents that abolish the acute migraine headache and agents aimed at prevention. The acutely acting antimigraine agents (5-HT(1B/1D) receptor agonists) stimulated research interest in the field of migraine. Currently prophylactic treatments for migraine include calcium channel blockers, 5-HT(2) receptor antagonists, beta-adrenoceptor blockers and gamma-amino butyric acid (GABA) agonists. Unfortunately, many of these treatments are non-specific and not always effective. Despite progress, the complex etiology of migraine requires further research, the condition often remains undiagnosed and available therapies are underused. In this review, the evidence that linked the different theories of migraine with its pathophysiology is considered. Furthermore, the present therapeutic targets and future approaches for the acute and prophylactic treatment of migraine are critically evaluated.

Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats.

Aqueous extract of leaves of M. oleifera was investigated and rationalised for its wound healing activity. The aqueous extract was studied at dose level of 300 mg/kg body weight using resutured incision; excision and dead space wound models in rats. Significant increase in wound closure rate, skin-breaking strength, granuloma breaking strength, hydroxyproline content, granuloma dry weight and decrease in scar area was observed. The prohealing actions seem to be due to increased collagen deposition as well as better alignment and maturation. From the results obtained, it may be concluded that the aqueous extract of M. oleifera has significant wound healing property.

Migraine: current concepts and emerging therapies.

Migraine is a recurrent incapacitating neurovascular disorder characterized by attacks of debilitating pain associated with photophobia, phonophobia, nausea and vomiting. Migraine affects a substantial fraction of world population and is a major cause of disability in the work place. Though the pathophysiology of migraine is still unclear three major theories proposed with regard to the mechanisms of migraine are vascular (due to cerebral vasodilatation), neurological (abnormal neurological firing which causes the spreading depression and migraine) and neurogenic dural inflammation (release of inflammatory neuropeptides). The modern understanding of the pathogenesis of migraine is based on the concept that it is a neurovascular disorder. The drugs used in the treatment of migraine either abolish the acute migraine headache or aim its prevention. The last decade has witnessed the advent of Sumatriptan and the 'triptan' class of 5-HT1B/1D receptor agonists which have well established efficacy in treating migraine. Currently prophylactic treatments for migraine include calcium channel blockers, 5-HT2 receptor antagonists, beta adrenoceptor blockers and gamma-amino butyric acid (GABA) agonists. Unfortunately, many of these treatments are non specific and not always effective. Despite such progress, in view of the complexity of the etiology of migraine, it still remains undiagnosed and available therapies are underused. In this article, the diverse pieces of evidence that have linked the different theories of migraine with its pathophysiology are reviewed. Furthermore, the present therapeutic targets and futuristic approaches for the acute and prophylactic treatment of migraine, with a special emphasis to calcitonin gene-related peptide, are critically evaluated.

Simultaneous determination of lamotrigine, phenobarbitone, carbamazepine and phenytoin in human serum by high-performance liquid chromatography.

A simple reversed-phase high-performance liquid chromatography (HPLC) method was developed for the simultaneous estimation of the antiepileptic drugs (AEDs) lamotrigine (LTG), phenobarbitone (PB), carbamazepine (CBZ) and phenytoin (PHT) in human serum. The procedure involves extraction of the AEDs by mixing 200 microl of serum with 200mul of acetonitrile containing 10 microg/ml of pentobarbitone as internal standard (IS). After centrifugation, 10 microl of the supernatant was injected onto a NOVA PAK C-18 column (250 mm x 4.6mm, 5 microm Hypersil ODS) and eluted with a mobile phase consisting of phosphate buffer (10 mM)-methanol-acetonitrile-acetone in the ratio of 55:22:12:11 (v/v) adjusted to pH 7.0. A UV detector set at 210 nm was employed for detection. The AEDs were well resolved from the human serum constituents and the internal standard. The method can quantify LTG, PB, CBZ, and PHT at concentrations as low as 0.2 microg/ml. The method was quantitatively evaluated in terms of linearity, accuracy, precision, recovery, selectivity, sensitivity, and specificity. The method is simple, convenient, and suitable for the analysis of AEDs from human serum.

Selective beta(1)-adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in rats.

The in-vivo beta-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against beta-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different &beta-adrenoreceptor subtypes (beta(1), beta(2) and beta(3)) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating beta(1), beta(2) and beta(3) adrenoreceptor blockade, respectively. The selectivity ratio for beta(1)/beta-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking beta(1)-adrenoreceptors and was more selective towards beta(1) receptors than to other beta-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have beta-adrenoreceptor blocking activity with high selectivity for the beta(1)-adrenoreceptor subtype.

Effect of Sapindus trifoliatus on hyperalgesic in vivo migraine models.

Phytotherapies have offered alternative sources of therapy for migraine and gained much importance in prophylactic treatment. Sapindus trifoliatus is a medium-sized deciduous tree growing wild in south India that belongs to the family Sapindaceae. The pericarp is reported for various medicinal properties. A thick aqueous solution of the pericarp is used for the treatment of hemicrania, hysteria or epilepsy in folklore medicine. We have investigated the antihyperalgesic effects of the lyophilized aqueous extract of S. trifoliatus in animal models predictive of experimental migraine models using morphine withdrawal-induced hyperalgesia on the hot-plate test and on 0.3% acetic acid-induced abdominal constrictions in adult male Swiss albino mice. The extract significantly (N = 10, P < 0.05) increased the licking latency in the hot-plate test when administered i.p. at 10 mg/kg (6.70 +/- 0.39 s in saline control vs 18.76 +/- 0.96 s in S. trifoliatus-treated animals) and significantly (N = 10, P < 0.001) reduced the abdominal constrictions when administered i.p. at 2 and 10 mg/kg (40.20 +/- 1.36 in saline control vs 30.20 +/- 1.33 and 23.00 +/- 0.98 for 2 and 10 mg/kg, i.p., respectively, in S. trifoliatus-treated animals). Furthermore, when administered i.p. at 20 and 100 mg/kg, the extract significantly (N = 10, P < 0.05) inhibited the apomorphine-induced climbing behavior in mice (climbing duration 15.75 +/- 5.0 min for saline control vs 11.4 +/- 1.28 and 3.9 +/- 1.71 min for 20 and 100 mg/kg, respectively, in S. trifoliatus-treated animals). In receptor radioligand-binding studies, the extract exhibited affinity towards D2 receptors. The findings suggest that dopamine D2 antagonism could be the mechanism involved in the antihyperalgesic activity of the aqueous extract of S. trifoliatus.

Pharmacological studies of the aqueous extract of Sapindus trifoliatus on central nervous system: possible antimigraine mechanisms.

The aqueous extract of pericarp of fruits of Sapindus trifoliatus (ST) Linn., family Sapindaceae was evaluated for its potential effects on central nervous system in mice. The extract at doses 20 and 100 mg/kg, i.p. significantly (p < 0.001) reduced the spontaneous locomotor activity and at 100 mg/kg, increased the thiopental-induced sleeping time. In rota-rod motor co-ordination test, ST at 100 mg/kg, i.p. significantly (p < 0.05-0.01) reduced the endurance time. Further ST exhibited no protection against maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced convulsions in mice. In receptor radioligand binding studies, ST exhibited affinity towards dopaminergic, alpha-adrenergic and muscarnic receptors. The findings suggest that, ST may possess principles with potential neuroleptic properties.