Amin Suria

Studies on the constituents of the leaves of Nerium oleander on behavior pattern in mice

Fresh, undried and uncrushed leaves of Nerium oleander were subjected to methanol extraction and bioassay directed fractionation. This led to the isolation of two purified fractions namely, B-1 and B-3. Fractions B-1 and B-3 were studied with respect to their actions on the central nervous system and behavior pattern in mice. Both fractions were found to produce reduction in locomotor activity, rota rod performance and potentiation of hexobarbital sleeping time. These fractions also showed analgesic activity. When tested against picrotoxin induced convulsions fraction B-1 showed 40% protection, while fraction B-3 exhibited 60% protection against bicuculline induced convulsions. These findings suggest that both fractions possess a CNS depressant action.

Anticonvulsant activities of ethanolic extract and aqueous fraction isolated from Delphinium denudatum

Dried roots of Delphinium denudatum Wall. are a popular folk remedy for the treatment of epilepsy in the traditional Unani system of medicine in the sub-continent. We carried out anticonvulsant screening of the ethanolic extract (EE) and aqueous fraction (AF) of this plant utilising the maximal electroshock (MEST) and subcutaneous pentylenetetrazole (scPTZ), bicuculline (scBIC), picrotoxin (scPTX) and strychnine (scSTN) tests for anticonvulsant activity. EE had weak dose-dependent anticonvulsant effects on seizures induced by PTZ and BIC. AF exhibited dose-dependent activity against hind limb tonic extension phase (HLTE) of MEST and comparatively stronger anticonvulsant activity against seizures induced by PTZ and BIC. The results suggest the presence of potent anticonvulsant compounds in AF of D. denudatum and deserve further investigation for isolation of active compounds and elucidation of the mechanism of anticonvulsant action.

Bio-active cardenolides from the leaves of Nerium oleander.

A bioactivity directed isolation of the methanolic extract of the fresh, uncrushed leaves of Nerium oleander showing a central nervous system (CNS) depressant effect in mice has been undertaken. As a result, four CNS depressant cardenolides including a new cardenolide, neridiginoside and three known constituents, nerizoside, neritaloside and odoroside-H, have been isolated which exhibited CNS depressant activity in mice at a dose of 25 mg/kg. The structure of neridiginoside was elucidated as 3 beta-O-(D-diginosyl)-5 beta, 14 beta-dihydroxy-card-20(22)-enolide, using spectroscopic methods including one-dimensional and two-dimensional NMR (COSY-45, NOESY, J-resolved, HMQC and HMBC). The known compounds have been indentified through spectral studies and comparison of data with those reported in the literature.

Differential effects of dimethyl sulfoxide on human platelet aggregation and arachidonic acid metabolism

DMSO inhibited human platelet aggregation induced by ADP, AA, PAF, or collagen in a concentration-related manner, in vitro. DMSO was a more effective inhibitor for aggregation induced by ADP and collagen than PAF or AA. However, in vivo experiments on rabbits showed that DMSO did not protect rabbits against death from pulmonary platelet thrombosis induced by AA. On the other hand, DMSO (1-30% v/v) had no effect on thromboxane production by platelets incubated with [14C]AA. Moreover, DMSO stimulated PGE2 production by bovine seminal vesicle PG synthase. DMSO also stimulated the production of 12-HETE but inhibited the production of tri-HETE produced via lipoxygenase pathway. Since lipoxygenase products play an important role in inflammation, our data suggest that the anti-inflammatory effects of DMSO are probably not mediated via its action on AA metabolism.

Evidence for involvement of amino acid neurotransmitters in anesthesia and naloxone induced reversal of respiratory paralysis

General anesthetics render a person unconscious and may produce respiratory paralysis at therapeutic doses. No pharmacological agent is available to restore respiration and the mechanism/s of anesthesia or apnea is not clearly understood. In this report, we present evidence to show that naloxone reversed respiratory failure induced by thiopental, ketamine, halothane but not that induced by phenobarbital. Furthermore, 25 mg/kg, i.v. thiopental, 140 mg/kg, i.v. ketamine, and 3% halothane produced anesthesia without significantly altering respiratory rate, increased GABA and decreased glutamate (except ketamine and phenobarbital) levels in rat brain stem and cortex, but not in caudate and cerebellum. Aspartate, glycine and alanine levels were not affected in four brain regions studied. Pretreatment with TSC for 30 minutes did not change GABA or glutamate contents, but abolished the anesthetic as well as the respiratory depressant actions of the anesthetics. Increasing the doses of anesthetics produced respiratory failure with further rise in GABA and fall in glutamate in brain stem and cortex. Naloxone reversed respiratory paralysis and restored GABA close to control values in rat brain stem and cortex with no changes in caudate or cerebellum. Data presented here suggest that GABA may be necessary to produce loss of consciousness and naloxone reverses anesthetic induced respiratory failure.

GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental

No agent is yet available to reverse respiratory paralysis produced by CNS depressants, such as general anesthetics. In this study naloxone reversed respiratory paralysis induced by thiopental in rats. 25 mg/kg, i.v. thiopental produced anesthesia without altering respiratory rate, increased GABA, decreased glutamate, and had no effect on aspartate or glycine levels compared to controls in rat cortex and brain stem. Pretreatment of rats with thiosemicarbazide for 30 minutes abolished the anesthetic action as well as the respiratory depressant action of thiopental. 50 mg/kg, i.v. thiopental produced respiratory arrest with further increase in GABA and decrease in glutamate again in cortex and brain stem without affecting any of the amino acids studied in four regions of rat brain. Naloxone (2.5 mg/kg, i.v.) reversed respiratory paralysis, glutamate and GABA levels to control values in brain stem and cortex with no changes in caudate or cerebellum. These data suggest naloxone reverses respiratory paralysis produced by thiopental and involves GABA in its action.

Chloramphenicol clearance in typhoid fever: implications for therapy.

We prospectively studied the pharmacokinetics of intravenous Chloramphenicol succinate (CS) in children (age 6 months-14 years) with culture proven typhoid fever (n=30) and non typhoidal illnesses (n=10). CS was administered in three different dosage regimens (50, 75 and 100 mg/kg/d-q 6 hourly). Liver function tests were monitored. Plasma trough and peak chloramphenicol concentrations were measured by HPLC analysis after 42 hrs. The 50 mg/kg/day dosage schedule was terminated midway through the study, as blood levels were consistently low and two patients with typhoid relapsed. children with typhoid has significantly lower clearance of CS in comparison with those with non-typhoidal illness (0.29±0.1 versus 0.5±0.37 1/kg/hr, P 0.05). There was no significant difference between mean peak and trough concentrations of chloramphenicol on 100 mg/kg/day and 75 mg/kg/day in children with typhoid. However, two children on 100 mg/kg/day dosage developed trough concentrations >20 mcg/ml. No correlation was found between CS clearance and serum bilirubin, SGPT (alanine transaminase) and alkaline phosphatase. Our data show altered clearance of CS in children with typhoid and suggests that 75 mg/kg/day may be a safer dose in children with hepatic dysfunction in typhoid.

Ability of human plasma to inhibit prostaglandin F2α in asthma

Human plasma has been reported to inhibit the conversion of arachidonic acid into prostaglandin (PG) E2 and PGF2 alpha. In the present study the plasma inhibitory activity was determined in three groups (16 each) of plasma obtained from normal healthy volunteers, treated asthmatics and untreated asthmatic patients. The result showed that plasma from all three groups were equally effective in inhibiting the biosynthesis of PGE2. Plasma of normal volunteers and treated asthmatics also inhibited PGF2 alpha biosynthesis. In contrast the plasma obtained from untreated asthmatics was considerably less active in inhibiting the biosynthesis of PGF2 alpha than plasma from the other two groups.