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Brain Res. 1997 Jun 20;760(1-2):238-42.
Chronic paroxetine desensitises 5-HT1D but not 5-HT1B autoreceptors in rat lateral geniculate nucleus.
Davidson C, Stamford JA.
Anaesthetics Unit (Neurotransmission Laboratory), St. Bartholomew's and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.
The present study examined the effect of chronic paroxetine (10 mg/kg p.o., 21 days) on the 5-HT1B and 5-HT1D autoreceptors controlling 5-HT efflux in slices of rat ventrolateral geniculate nucleus. Electrically stimulated 5-HT efflux (10 pulses, 200 Hz, 0.1 ms, 10 mA) was measured using fast cyclic voltammetry. Peak 5-HT efflux was greater (P < 0.01) after chronic paroxetine (22.2 +/- 1.4 nM, mean +/- S.E.M.) than water (15.8 +/- 1.4 nM). 5-HT efflux was inhibited by CP 93129 (1 nM-10 microM) and sumatriptan (1 nM-1 microM), agonists at 5-HT1B and 5-HT1D receptors, respectively. Chronic paroxetine did not affect the sensitivity of the 5-HT1B autoreceptor but shifted the sumatriptan concentration-response curve to the right (P < 0.05). These data suggest that chronic paroxetine increases evoked 5-HT efflux. This may be the result of desensitisation of 5-HT1D but not 5-HT1B autoreceptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9237540&dopt=Abstract
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Brain Res Bull. 1997;43(4):405-9.
Synergism of 5-HT 1B/D antagonists with paroxetine on serotonin efflux in rat ventral lateral geniculate nucleus slices.
Davidson C, Stamford JA.
Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.
Serotonin (5-HT) efflux in rat ventral lateral geniculate nucleus (vLGN) slices was evoked by electrical stimulation (20 pulses at 100 Hz, 10 mA, 190 ms train) and measured, along with 5-HT uptake, by fast cyclic voltammetry at implanted carbon fibre microelectrodes. Paroxetine (100 nM), a selective serotonin reuptake inhibitor (SSRI), increased stimulated 5-HT efflux to 194 +/- 25% of pre-drug values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 684 +/- 135%. When given alone, neither the selective 5-HT 1B antagonist isamoltane (1 microM) nor the 5-HT 1D/B antagonist GR 127935 (50 nM), affected 5-HT efflux or uptake under this stimulation paradigm. When added in combination with paroxetine, both isamoltane and GR 127935 significantly potentiated the effect of paroxetine on stimulated 5-HT efflux: isamoltane to 302 +/- 48% at maximum (p < 0.05 vs. paroxetine alone), GR 127935 to 318 +/- 95% (p < 0.05 vs. paroxetine alone) of pre-drug values. Neither isamoltane nor GR 127935 had any effect on 5-HT uptake. The selective 5-HT 1A antagonist WAY 100635 (10 nM) had no effect on 5-HT efflux or uptake, alone or in combination with paroxetine. These data suggest that, under these experimental conditions, paroxetine gives rise to tonic activation of the vLGN terminal 5-HT autoreceptors. Furthermore, these data show that 5-HT 1B and possibly 5-HT 1D antagonists block this inhibitory autoreceptor tone and may thus be a useful addition to SSRI treatment in the clinic.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9241443&dopt=Abstract
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Somatosens Mot Res. 1997;14(1):27-33.
Contributions of raphe-cortical and thalamocortical axons to the transient somatotopic pattern of serotonin immunoreactivity in rat cortex.
Bennett-Clarke CA, Chiaia NL, Rhoades RW.
Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo 43699, USA.
Two experiments were carried out to evaluate the relative contributions of thalamocortical and raphe-cortical fibers to the transient somatotopically organized pattern of serotonin (5-HT) immunoreactivity that appears in the primary somatosensory cortex (SI) of rats during the first 2 weeks of life. In the first experiment, the specific 5-HT uptake inhibitors, fluoxetine and paroxetine, were administered systemically, animals were killed 3, 6, or 12 h later, and cortices evaluated for 5-HT immunoreactivity. Fluoxetine treatment had no appreciable effect on the density of 5-HT immunoreactivity in the cortex. Paroxetine treatment caused a reduction in 5-HT immunoreactivity which was maximal 6 h after administration. Examination of the cortices of these animals revealed a loss of very fine dust-like 5-HT immunoreactivity, but a vibrissae-related pattern remained visible in thicker fibers. In a second experiment, raphe-cortical fibers were destroyed by systemic administration of 5,7-dihydroxytryptamine on the day of birth. Six days after this manipulation, 5-HT was applied directly to the cortex in vivo and the animals were then killed and cortices processed to demonstrate 5-HT immunoreactivity. The cortices of these rats revealed a fine dust-like immunoreactivity organized in a somatotopic pattern, but only very few 5-HT-positive axons. The results of these experiments suggest that both raphe-cortical axons and thalamocortical fibers contribute to the patterned 5-HT immunoreactivity observed in SI of perinatal rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9241726&dopt=Abstract
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