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At least 1,117 records · Page 62Linked to original sources
PubMed1996

Venlafaxine hydrochloride (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy.

Venlafaxine hydrochloride (Effexor) is a structurally novel antidepressant that inhibits reuptake of 5-hydroxytryptamine and noradrenaline, but unlike the older antidepressants, has few side-effects. The objective of this study was to determine whether venlafaxine relieves thermal hyperalgesia in rats with neuropathic pain due to chronic constriction injury (CCI) of the sciatic nerve. Paw withdrawal latency (PWL) to heat was tested for each hind paw. A painful neuropathy was induced in 24 male Sprague-Dawley rats (Group 1) as described by Bennett and Xie. Rats randomly received either oral venlafaxine (22 mg/kg) or placebo via gavage feeding beginning the day after surgery. Postoperative PWL testing began 3 days after CCI (Time 0). A second group of 12 rats (Group 2) was used to confirm that venlafaxine reverses hyperalgesia in rats with a fully developed neuropathic lesion. These animals began to receive oral venlafaxine (22 mg/kg) starting on the third postoperative day, after the presence of thermal hyperalgesia was verified through PWL testing. Testing was continued for 5 days, during venlafaxine administration. A third group of 12 rats (Group 3) had activity measured before and after treatment with venlafaxine (22 mg/kg). Rats in the placebo group developed thermal hyperalgesia while those that received venlafaxine did not. Venlafaxine also appeared to have a mild non-specific analgesic effect that increased PWL in the sham limb. In Group 2, thermal hyperalgesia was present on day 3, but following treatment with venlafaxine, thermal hyperalgesia resolved. Activity measurements confirmed that venlafaxine was not sedating in this rat model.

Administration, Oral↗
PubMed2001

Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use.

A number of studies suggested that cannabis use can cause or exacerbate psychoses and may increase the risk of developing schizophrenia. These findings suggest that changes in the cannabinoid system of the brain may be involved in the pathology of schizophrenia. To determine whether changes in the cannabinoid system were present in the brains of subjects with schizophrenia, we used in situ radioligand binding and autoradiography to measure the binding of [3H]CP-55940 to the cannabinoid-1 receptor in the dorsolateral prefrontal cortex (Brodmann's area 9), caudate-putamen and areas of the temporal lobe from schizophrenic and control subjects, some of whom had ingested cannabis close to death. There was an increase in the density of [3H]CP-55940 binding to cannabinoid-1 receptors in the dorsolateral prefrontal cortex from subjects with schizophrenia (mean+/-S.E.M.: 142+/-9.9 vs 119+/-6.6fmol/mg estimated tissue equivalents; P<0.05) that was independent of recent cannabis ingestion. There was an increase in the density of cannabinoid-1 receptors in the caudate-putamen from subjects who had recently ingested cannabis (151+/-9.0 vs 123+/-7.2fmol/mg estimated tissue equivalents; P<0.05) that was independent of diagnoses. These data indicate that there are changes in cannabinoid-1 receptors in the dorsolateral prefrontal cortex that may prove to be associated with the pathology of schizophrenia. By contrast, changes in the density of cannabinoid-1 receptors may occur in the caudate-putamen in response to cannabis ingestion.

Brain↗
PubMed2002

Cannabinoids attenuate depolarization-dependent Ca2+ influx in intermediate-size primary afferent neurons of adult rats.

CB1 receptors have been localized to primary afferent neurons, but little is known about the direct effect of cannabinoids on these neurons. The depolarization-evoked increase in the concentration of free intracellular calcium ([Ca(2+)](i)), measured by microfluorimetry, was used as a bioassay for the effect of cannabinoids on isolated, adult rat primary afferent neurons 20-28 h after dissociation of dorsal root ganglia. Cannabinoid agonists CP 55,940 (100 nM) and WIN 55,212-2 (1 microM) had no effect on the mean K(+)-evoked increase in [Ca(2+)](i) in neurons with a somal area<800 microm(2), but the ligands attenuated the evoked increase in [Ca(2+)](i) by 35% in neurons defined as intermediate in size (800-1500 microm(2)). The effects of CP 55,940 and WIN 55,212-2 were mediated by the CB1 receptor on the basis of relative effective concentrations, blockade by the CB1 receptor antagonist SR141716A and lack of effect of WIN 55,212-3. Intermediate-size neurons rarely responded to capsaicin (100 nM). Although cannabinoid agonists generally did not inhibit depolarization-evoked increases in [Ca(2+)](i) in small neurons, immunocytochemical studies indicated that CB1 receptor-immunoreactivity occurred in this population. CB1 receptor-immunoreactive neurons ranged in size from 227 to 2995 microm(2) (mean somal area of 1044 microm(2)). In double labeling studies, CB1 receptor-immunoreactivity co-localized with labeling for calcitonin gene-related peptide and RT97, a marker for myelination, in some primary afferent neurons. The decrease in evoked Ca(2+) influx indicates that cannabinoids decrease conductance through voltage-dependent calcium channels in a subpopulation of primary afferent neurons. Modulation of calcium channels is one mechanism by which cannabinoids may decrease transmitter release from primary afferent neurons. An effect on voltage-dependent calcium channels, however, represents only one possible effect of cannabinoids on primary afferent neurons. Identifying the mechanisms by which cannabinoids modulate nociceptive neurons will increase our understanding of how cannabinoids produce anti-nociception in normal animals and animals with tissue injury.

Age Factors↗
PubMed2003

Antidepressant drug treatment induces Arc gene expression in the rat brain.

The mechanism underlying the therapeutic effect of antidepressants is not known but neuroadaptive processes akin to long-term potentiation have been postulated. Arc (Activity-regulated, cytoskeletal-associated protein) is an effector immediate early gene implicated in LTP and other forms of neuroplasticity. Recent data show that Arc expression is regulated by brain 5-hydroxytryptamine neurones, a target of many antidepressants. Here in situ hybridisation and immunohistochemistry were used to examine whether Arc expression in rat brain is altered by antidepressant drug treatment. Repeated administration of the monoamine reuptake inhibitors paroxetine, venlafaxine or desipramine induced region-specific increases in Arc mRNA. These increases were greatest in regions of the cortex (frontal and parietal cortex) and hippocampus (CA1 layer) and absent in the caudate putamen. Repeated treatment with the monoamine oxidase inhibitor, tranylcypromine, increased Arc mRNA in a similar fashion to the monoamine reuptake inhibitors. The antidepressant drugs also increased the number of Arc-immunoreactive cells in the parietal cortex. Acute antidepressant injection, and repeated administration of the antipsychotic drug chlorpromazine, produced either limited or no changes in Arc mRNA. The data suggest that chronic treatment with antidepressant drugs induces Arc gene expression in specific regions across the rat forebrain. Up-regulation of Arc expression may be part of the process by which antidepressant drugs achieve long-term changes in synaptic function in the brain.

Animals↗
PubMed1999

Cannabinoid receptors undergo axonal flow in sensory nerves.

Cannabinoids modulate nociceptive processing through central and peripheral mechanisms. The present study was conducted to evaluate axonal flow of cannabinoid receptors from the dorsal root ganglion to the periphery and to identify the putative involvement of CB1 and/or CB2 receptor subtypes. The sciatic nerve was tightly ligated to dam the flow of cannabinoid receptors to the periphery. The densities of cannabinoid receptors proximal and distal to one or two tightly constrictive ligatures was evaluated using in vitro receptor binding and high-resolution emulsion autoradiography. In both models, [3H]CP55,940 binding accumulated proximal as opposed to distal to the ligature. These data indicate that axonal transport of cannabinoid receptors to the periphery was occluded by tight constriction of the sciatic nerve. In situ hybridization histochemistry revealed that dorsal root ganglia cells synthesize CB1 but not CB2 receptor messenger RNA. By contrast, CB2 messenger RNA was highly expressed in sections of rat spleen that were processed together with the dorsal root ganglia, as previously described. These data demonstrate that neuronal cannabinoid CB1 receptors are synthesized in cells of the dorsal root ganglia and inserted on terminals in the periphery.

Animals↗
PubMed2000

Olfactory experience decreases responsiveness of the olfactory bulb in the adult rat.

We recently reported the existence of dramatic modifications of the olfactory bulb reactivity following a very simple manipulation of the olfactory input as an exposure to an odorant. The present study aimed at testing the possibility that such effects could depend on the nature of the exposure odour. For this purpose, rats were exposed 20 min per day during six consecutive days to cineole, methyl-amyl ketone, isoamyl acetate or with no odour in the control group. On day 7, rats were anaesthetized and the spontaneous activity of mitral/tufted cells was recorded along with their responses to the familiar odour and to four novel odours. Results revealed that: (i) the firing frequencies were not significantly different in the four groups; (ii) the proportion of excitatory responses was considerably decreased in the exposed groups while the number of non-responses was significantly enhanced; (iii) excitatory responses were decreased not only to the familiar odour but also to four other novel odours; (iv) this lower responsiveness was long lasting at least for isoamyl acetate exposure; and (v) increasing concentration of test odours was not enough to allow mitral/tufted cells to recover control responsiveness. All of these effects have a differential importance according to the exposure odour. In particular, the more powerful an odour is in activating control cells, the more non-specific the decrease in mitral/tufted cell reactivity is. Hypotheses on the underlying mechanisms are advanced.

Action Potentials↗
PubMed1998

Venlafaxine-tramadol similarities.

Venlafaxine and tramadol are relatively new compounds indicated for the treatment of depression and pain, respectively. These agents share a number of molecular and pharmacological features that may allow for broader and overlapping therapeutic indications for both drugs. Additionally, certain patient populations with coexisting depression and pain syndromes could potentially be treated with a single agent.

Analgesics, Opioid↗
PubMed2002

Constituents of aromatic plants: eucalyptol.

The subacute toxicity studies reported up to now in rats and mice suggested that mice were less susceptible than rats to the toxicity of eucalyptol. In fact, after gavage, it was found toxic in male rats at doses higher than 600 mg/kg while no effect was seen in mice up to 1200 mg/kg. However, the limitations and the quality of the study do not allow the extrapolation of a 'no effect level'. Several reports in rat and brushtail possum show the formation of hydroxylated bicycled products of eucalyptol as main metabolites. Moreover, metabolites which require ring opening have been also detected. Following the accidental exposure of human beings, death was reported in two cases after ingestion of 3.5-5 ml of essential eucalyptus oil, but a number of recoveries have also been described for much higher amounts of oil.

Animals↗
PubMed1997

Characterization of anandamide-induced tolerance: comparison to delta 9-THC-induced interactions with dynorphinergic systems.

The endogenous ligand for the cannabinoid receptor, arachidonylethanolamide (anandamide), has been shown to produce antinociception using the tail-flick test following intrathecal administration. Anandamide was administered i.p. (40 mg kg) to mice four times per day for 3 days. Tolerance developed to anandamide: the ED50 for anandamide (i.t.) was shifted from 40 (26-61) to 139 (79-248) micrograms/mouse. Anandamide-tolerant mice were cross-tolerant to delta 9-THC and CP55,940, but not cross-tolerant to mu-, delta- or kappa- opioids, including dynorphins. Conversely, delta 9-THC-tolerant mice are cross-tolerant to anandamide, CP55,940 and kappa agonists. Our data indicate that anandamide and delta 9-THC differ in the mechanisms by which they induce tolerance, in particular the interaction with endogenous dynorphinergic systems.

Analgesics↗
PubMed2000

A tyramine receptor gene mutation causes a defective olfactory behavior in Drosophila melanogaster.

We characterized molecular profiles of a new olfactory mutant line, honoka (hono), which was found among 500 viable P-element insertion lines screened first by 5-bromo-4-chloro-3-indrolyl-beta-D-galactopyranoside (X-gal) staining on the third segment of the antenna, and then by behavioral assays to several pure chemicals. The behavioral responses of hono mutants to repellents such as ethyl acetate (EA), benzaldehyde (BZ) and 4-methylcycrohexanol (MCH), were reduced compared with those of a control strain. The location of the P-element insertion was determined to be about 100bp) upstream of the first exon of the tyramine receptor gene. The level of 3.6kb tyramine receptor mRNA expression was reduced in hono compared with that of wild-type flies. The tyramine receptor cDNA hybridized to the chromosomal division 79C-D, the same locus as the P-element insertion point in hono, and not to 99A-B, previously reported by Arakawa et al. (1990. Neuron 2, 343-354). Electrophysiological responses to octopamine and tyramine were examined by measuring the excitatory junctional potential (EJP) amplitude from larval body-wall muscles of the hono mutant. The hono was impaired with responding to tyramine, while displaying normal response to octopamine. These results indicate that tyramine has a functional role in the Drosophila olfactory system as a neurotransmitter or a neuromodulator, and hono is the first tyramine receptor mutant. This study provides the first step toward understanding of the molecular genetics of tyramine-mediated neural functions in Drosophila.

Acetates↗
PubMed2003

Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli.

The present investigation aimed to compare trigeminal nasal function of anosmic and hyposmic patients to healthy controls. Further, we aimed to study effects of age and gender on trigeminally mediated sensations following intranasal chemosensory stimulation. Participants were 35 patients with olfactory dysfunction (n=13: functional anosmia; n=22: hyposmia; age 28-69 years, mean age 56 years). Their results were compared with 17 normosmic subjects (28-82 years, mean 52 years). To analyze effects of age and gender in healthy subjects, an additional 24 healthy subjects were included (19-27 years; mean 24 years). Olfactory function was assessed using the 'Sniffin' Sticks' test kit (butanol odor threshold, odor discrimination, odor identification). The subjects' ability to lateralize odors was investigated for benzaldehyde and eucalyptol. Patients with olfactory dysfunction had lower scores in the lateralization task than controls (P<0.001) indicating decreased trigeminal sensitivity. Among anosmic patients scores were not different in relation to different causes of olfactory dysfunction (P>0.29). There was a weak, but significant, correlation between localization of eucalyptol and duration of olfactory dysfunction (P=0.017). When investigating normosmic subjects only, no gender-related difference was apparent for lateralization scores. However, older subjects had lower scores than younger ones (P<0.01). Results of partial correlational analyses controlling for age suggested a relation between the trigeminal and the olfactory systems. In conclusion, results of the present study indicate that patients with olfactory dysfunction have lower trigeminal sensitivity compared with normosmic controls. This seems to be independent of the cause of olfactory loss. The deficit appears to improve with duration of the olfactory dysfunction, possibly indicating adaptive mechanisms. Further, the data suggest an age-related decrease of intranasal trigeminal sensitivity in healthy subjects. Analyses additionally indicate a correlation between olfactory and trigeminal sensitivity.

Adult↗
PubMed1986

Determination of tramadol in human serum by capillary gas chromatography with nitrogen-selective detection.

A specific, sensitive and precise method for the determination of tramadol in human serum is described. It comprises a three-step extraction procedure and a specific determination by capillary gas chromatography with nitrogen-selective detection, using a homologue of tramadol as an internal standard. The specificity of the method was checked by gas chromatography-mass spectrometry. Precision parameters were 1.7-5.5% (within-run) and 3.2-5.7% (between-run) in the concentration range 12.5-200 ng/ml. The detection limit was about 3 ng/ml.

Chromatography, Gas↗
PubMed1985

Quantitative determination of tramadol in human serum by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method for the quantitative determination of tramadol in human serum, plasma or whole blood samples is described. The method involves the use of [2H2, 15N]tramadol hydrochloride as an internal standard and chemical ionization with isobutane, employing single-ion monitoring for quantification. It is specific, sensitive and precise, and has high accuracy. The within-run coefficient of variation is about 1% between 25 and 200 ng/ml and 1.8-2.9% at the lowest concentrations tested (6.25 and 12.5 ng/ml). The between-run coefficient of variation increases from 1.6% to 5.2% with decreasing concentration from 200 to 12.5 ng/ml. The calibration graphs were linear in the tested concentration range, and the accuracy of the assay was not dependent on the sample volume used. The detection limit was about 4 ng/ml for serum samples of 1 ml. The method proved suitable for pharmacokinetic studies. Its high sensitivity allows measurements of serum concentrations for at least 30 h after the single administration of therapeutic doses of tramadol hydrochloride.

Biotransformation↗
PubMed2001

Rapid high-performance liquid chromatographic measurement of venlafaxine and O-desmethylvenlafaxine in human plasma. Application to management of acute intoxications.

Venlafaxine, a second-generation antidepressant, acts by inhibition of the reuptake of presynaptic noradrenaline and serotonin. The main metabolite, O-desmethylvenlafaxine was found biologically active. For toxicological purpose, a rapid specific and accurate RP-HPLC assay was developed for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma. A linear response was observed over the concentration range 0.2-4 microg/ml. A good accuracy (<8%) was achieved for all quality controls, with intra-day and inter-day variation coefficient less than 10%. Finally, no interference was observed with other psychotic drugs encountered in acute poisoning. This rapid method (run time <10 min) was used to manage four voluntary intoxications involving venlafaxine.

Antidepressive Agents, Second-Generation↗
PubMed1997

Rapid determination of venlafaxine and O-desmethylvenlafaxine in human plasma by high-performance liquid chromatography with fluorimetric detection.

A rapid and sensitive high-performance liquid chromatographic technique for simultaneous measurement of plasma venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) is described. The process begins with the extraction of VEN and ODV, with maprotiline (MAP) as internal standard, from human plasma into an intermediate organic mixture of hexane-isoamyl alcohol and finally into an aqueous solution of 0.05% phosphoric acid. Isocratic separation of VEN, ODV and MAP is carried out by utilizing a reversed-phase butyl-bonded column (C4/E) with mobile phase consisting of acetonitrile and 40 mM phosphate buffer, pH 6.8 (50:50, v/v). Detection of VEN, ODV and MAP is done by mean of fluorimetry with excitation and emission wavelengths set at 276 and 598 nm, respectively. As low as 1.0 ng/ml VEN is detectable; while the limit of detection for ODV is 5 ng/ml. C.V. (%) of intra-day samples for both VEN and ODV are less than 10% at three concentrations tested (10.0, 50.0, 100.0 ng/ml). Similarly, over the same nominal concentrations, the precision of inter-day (5 days) samples also results in C.V. (%) smaller than 10% for both compounds, except for ODV measured at 10 ng/ml (C.V.<15%). Approximately, 100% VEN can be extracted from plasma; whereas, for ODV the recovery rate is nearly 70%. This present method is rapid, sensitive, accurate and simple for routine clinical monitoring of plasma VEN and its major metabolite ODV.

Antidepressive Agents, Second-Generation↗
PubMed1998

Simultaneous measurement of venlafaxine and its major metabolite, oxydesmethylvenlafaxine, in human plasma by high-performance liquid chromatography with coulometric detection and utilisation of solid-phase extraction.

Venlafaxine, oxydesmethylvenlafaxine and an internal standard (paroxetine) were extracted from plasma by a solid-phase extraction technique. Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric endpoint detection. The standard curves were linear over the range 0-200 ng/ml for both venlafaxine and oxydesmethylvenlafaxine in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 10%. The absolute recovery averaged 74% for venlafaxine and 67% for oxydesmethylvenlafaxine. The sensitivity was 0.5 ng for both the analytes. Plasma profiles of the analytes following oral administration of venlafaxine, are presented.

Administration, Oral↗
PubMed2002

Microwave-assisted preparation of cyclic ketals from a cineole ketone as potential cosmetic ingredients: solvent-free synthesis, odour evaluation, in vitro cytotoxicity and antimicrobial assays.

Some cyclic ketals derived from (+)1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one were obtained in excellent yields by microwave activation under solvent-free conditions, as a 'green chemistry' procedure. The results obtained using acidic alumina containing 7% p-toluenesulfonic acid, as mineral support, are reported and compared with those obtained by classical methods. The new compounds were tested for their olfactive character and for a potential cosmetic use. In vitro skin cytotoxicity tests were carried out on the most promising compounds, by using NCTC 2544 human keratinocytes as target cells. They all displayed slight cytotoxic effects which were one order of magnitude lower than those found with sodium dodecylsulphate positive control. Two compounds that resulted interesting as toothpaste aromas, were submitted to antimicrobial assays and showed their activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus hominis, Propionibacterium acnes and Candida albicans.

Anti-Infective Agents↗
PubMed2001

Physicochemical investigations on microemulsification of eucalyptol and water in presence of polyoxyethylene (4) lauryl ether (Brij-30) and ethanol.

The microemulsification of eucalyptol/polyoxyethylene(4)lauryl ether (Brij-30)/ethanol/water has been investigated. The phase behaviours of the mixed system in pseudoternary and tetrahedral representations have been examined to understand the topological nature of the multicomponent mixtures. Phase volumes of the heterogeneous combinations have been estimated to understand the mixing efficacy of the combinations. Shear viscosities of different monophasic compositions have been measured at different shear rates and temperatures, and the activation parameters for the viscous flow have been evaluated. The dimensions of the nanodispersions of w/o and o/w types, their diffusion coefficients and the polydispersity have been determined by the DLS method. The energetics of solubilisation (dissolution) of water in oil+Brij-30+ethanol as well as oil in water+Brij-30+ethanol forming w/o and o/w microemulsions, respectively, have been calorimetrically determined. Considering the phase separation point to be the point of maximum solubility, the energetic parameters (enthalpy, free energy and entropy) of the microemulsification process have been estimated.

Calorimetry↗