Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour. (1/63)

The essential oil from Piper solmsianum leaves and its major compound (sarisan) were tested to verify their influences upon mice behaviour. The essential oil was obtained by hydrodistillation in a modified Clevenger extractor and analysed by GC/ MS. This analysis revealed in the oil the presence of monoterpenes, sesquiterpenes and of arylpropanoids. The compound sarisan, a myristicin analogue, was isolated from the oil to perform the pharmacological tests. Emulsions of the oil and of sarisan (5.0 and 10.0% v/v) were used in the tests. Pentobarbital (30 mg/ kg s.c.) or diazepam (2.5 mg/ kg s.c.) were tested as standard drugs to verify depressant or anxiolytic effects, respectively. Both essential oil and sarisan showed to have exciting and depressant effects in the tested animals.  (+info)

The ability of environmental context to facilitate psychomotor sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and on conditioned responding. (2/63)

Doses of amphetamine or cocaine that fail to induce psychomotor sensitization when given to a rat in its home cage can produce robust sensitization if given immediately following placement into a relatively novel, distinct environment. A drug-associated context can serve as a conditioned stimulus, and therefore may promote robust sensitization by facilitating associative learning processes. We examined this hypothesis by habituating rats to the test environment for 1 or 6--8 hr prior to each drug injection, which degrades the ability of environmental context to serve as an effective conditioned stimulus. When 0.5 mg/kg of amphetamine was administered intravenously immediately after placement into a distinct environment there was a large acute psychomotor response (rotational behavior) on the first test day, and robust sensitization developed with repeated daily injections. When the same treatment was administered in the home cage, there was a small acute response and no sensitization developed. The enhanced acute response seen in the distinct environment was significantly attenuated by 1 hr of habituation to the test environment, and completely abolished by 6--8 hr of habituation. Also, as little as 1 hr of habituation completely prevented the development of a conditioned rotational response. In contrast, neither 1 nor 6--8 hr of habituation had any effect on the ability of amphetamine to induce robust behavioral sensitization. It is concluded that the ability of a distinct environment to facilitate sensitization to amphetamine can be dissociated from its effect on acute drug responsiveness and from the ability of drug-associated environmental stimuli to elicit a conditioned response. Possible mechanisms by which a distinct environment facilitates sensitization are discussed.  (+info)

Bronchodilator therapy and hyperactivity in preschool children. (3/63)

The common report of parents of asthmatic children that inhaled/nebulised salbutamol causes overactive behaviour was investigated. Nineteen children were assessed in a standardised setting before and after the administration of nebulised salbutamol and placebo. Neither parental report nor observer ratings suggested any significant increase in the child's level of activity.  (+info)

The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide. (4/63)

AIMS: Morphine-6-glucuronide (M6G), one of the active metabolites of morphine, has attracted considerable interest as a potent opioid analgesic with an apparently superior therapeutic index. To date studies have used the intravenous route, which is generally unacceptable in the treatment of cancer related pain. The aim of this study was to define the pharmacokinetics, toxicity and cardio-respiratory effects of three alternative routes of administration of M6G. METHODS: Ten healthy volunteers participated in an open randomized study. Subjects received M6G 2 mg as an intravenous bolus, 20 mg orally, 2 mg subcutaneously and 4 mg by the nebulized route. Pulse, blood pressure, respiratory rate and peak flow rate were monitored and subjective toxicity recorded on rating and visual analogue scales. RESULTS: After i.v. M6G the mean (+/- s.d.) AUC(0,infinity) standardized to a dose of 1 mg was 223 +/- 57 nmol l(-1) h, mean elimination half-life was 1.7 +/- 0.7 h and the mean clearance was 157 +/- 46 ml min(-1). These parameters were virtually identical after subcutaneous administration which had a bioavailability (F(0,infinity)) of 102 +/- 35% (90% CI 82, 117%) and t(max) of 0.5 +/- 0.2 h. The mean bioavailability of nebulized M6G was 6 +/- 2% (90% CI 4, 7%) with a t(max) of 1.2 +/- 0.8 h. Following oral M6G two plasma M6G peaks were seen in 7 of the 10 subjects, the first with a t(max) of 3.1 (+/- 0.9) h. The second peak had a t(max) of 13.4 (+/-5.0) h, started approximately 4 h after dosing, and was associated with the detection of plasma M3G and morphine, suggesting that M6G was significantly hydrolysed in the gut to morphine, which was then glucuronidated following absorption. Although the overall mean bioavailability was 11 +/- 3% (90% CI 9, 12%), confining the analysis to data from the first peak suggested a bioavailability of directly absorbed M6G of only 4 +/- 4%. Apart from a characteristic dysphoria following intravenous and subcutaneous M6G, there was no significant toxicity. CONCLUSIONS: With the minimal toxicity reported in this and previous studies, subcutaneous infusion of M6G may potentially provide clinically useful analgesia for advanced cancer pain. Nebulized M6G is not significantly absorbed via the lungs, and if opiates are shown to have a local effect in the lung, reducing the sensation of breathlessness, then nebulized administration is likely to minimize systemic effects. Oral M6G has poor bioavailability, but is significantly hydrolysed in the gut to morphine, which is subsequently glucuronidated following absorption. This circuitous route accounts for the majority of systemically available M6G after oral administration.  (+info)

Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children. (5/63)

BACKGROUND: In children, sevoflurane anaesthesia is associated with postanaesthetic agitation, which is treated mainly with opioids. We compared the effectiveness of epidural and i.v. clonidine in the prevention of this postanaesthetic agitation. METHODS: Eighty children aged 3-8 yr (ASA I-II) received standardized general anaesthesia with inhaled sevoflurane and caudal epidural block with 0.175% bupivacaine 1 ml kg-1 for minor surgery. The children were assigned randomly to four groups: (I) clonidine 1 microgram kg-1 added to caudal bupivacaine; (II) clonidine 3 micrograms kg-1 added to caudal bupivacaine; (III) clonidine 3 micrograms kg-1 i.v. and caudal bupivacaine; and (IV) caudal block with bupivacaine, no clonidine (control). A blinded observer assessed the behaviour of the children during the first postoperative hour. Secondary end-points were the time to fitness for discharge from the postanaesthesia care unit, and haemodynamic and respiratory variables. RESULTS: The incidence of agitation was 22, 0, 5 and 39% in groups I, II, III and IV respectively (P < 0.05 for groups II and III compared with group IV). During the first hour after surgery, patients in groups II and III had significantly lower scores for agitation than group IV patients. Time to fitness for discharge did not differ between the four groups. CONCLUSIONS: Clonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it.  (+info)

Nithsdale Schizophrenia Surveys 23: movement disorders. 20-year review. (6/63)

BACKGROUND: In the past 10 years the new atypical antipsychotic drugs have stimulated further interest in the pharmacological management of schizophrenia. The risk of movement disorders has been reported to be less with these new agents. AIMS: To examine the current prevalence of movement disorders among all people with schizophrenia in a discrete geographical area, to compare the prevalence in patients receiving and not receiving atypical antipsychotic drugs; and to compare current prevalence with prevalence over the past 20 years. METHOD: In Nithsdale, south-west Scotland, in 1999/2000, we replicated previous studies by using the Abnormal Involuntary Movements Scale, Simpson-Angus scale and Barnes Akathisia Rating Scale to measure tardive dyskinesia, parkinsonism and akathisia, respectively. Mental state was assessed by the Positive and Negative Syndrome Scale. RESULTS: In 136 patients the prevalence of probable tardive dyskinesia was 43%, of parkinsonism 35% and of akathisia 15%. Parkinsonism was present as often in those receiving atypicals as in those receiving standard oral antipsychotics. The prevalence of tardive dyskinesia has doubled over 20 years. CONCLUSIONS: Movement disorders remain significant problems for patients despite the introduction of atypical antipsychotic drugs.  (+info)

Akathisia--diagnostic dilemma and behavioral treatment. (7/63)

Akathisia, an involuntary movement disorder resulting from exposure to antipsychotics, is characterized by subjective restlessness and a strong desire to move about. The diagnosis is often complicated by the overlapping symptoms of pseudoakathisia, chronic akathisia and tardive dyskinesia. This report deals with a patient with schizophrenia who developed akathisia after exposure to antipsychotics. Later, she developed movements that were more like pseudoakathisia and tardive dyskinesia rather than acute akathisia. On failure of anti-akathisia medication, she was treated with a behavioral regime to which her akathisia responded. This behavioral regime used the technique of distraction as a primary tool. This case report highlights the diagnostic difficulties in akathisia and the application of behavioral treatment for akathisia that is non-responsive to anti-akathisia medication.  (+info)

The effects of temporary inactivation of the core and the shell subregions of the nucleus accumbens on prepulse inhibition of the acoustic startle reflex and activity in rats. (8/63)

The nucleus accumbens can be dissociated into at least two subregions: a 'core' and a 'shell'. Using temporary chemical inactivation of these subregions, we investigated whether they are differentially involved in the regulation of prepulse inhibition (PPI) of the acoustic startle reflex and activity. For this purpose, rats were bilaterally implanted with guide cannulae aimed at either the core or the shell and infused with the GABA(A) receptor agonist muscimol (0.5 microg/0.2 microl per side). The control group consisted of vehicle infused and unoperated rats. To ascertain the region selectivity of the infusions, 0.2 microl of [3H]muscimol was infused into either the core or the shell of an additional group of rats. The behavioral results demonstrated that in comparison to the control group, inactivation of the core led to a loss of the prepulse intensity dependency of PPI. Moreover, core inactivation resulted in akinesia directly after infusion, but in hyperactivity 24 and 72 h thereafter in contrast to the control group. In both experiments, inactivation of the shell was ineffective compared to controls. Analysis of the autoradiograms revealed that the spread of drug into the other subregion was minimal, supporting the region selectivity of the inactivation. These results lend further support to the existence of a functional dissociation between the core and the shell, with the former being preferentially involved in PPI and locomotion. The persistent hyperactivity after the muscimol infusion into the core could be explained by compensatory mechanisms taking place in the nucleus accumbens.  (+info)

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