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Nihon Shinkei Seishin Yakurigaku Zasshi. 1998 Feb;18(1):19-21.
Effects of washing procedure on platelets pretreated with serotonin uptake inhibitors in vitro: low Ki values predict long-lasting inhibition of serotonin uptake in vivo.

Ishigooka J, Kasahara T, Nagata E, Murasaki M, Miura S.

Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan.

The effect of a washing procedure on serotonin (5-HT) uptake in vitro was investigated using human platelets pretreated with nine 5-HT uptake inhibitors and various Ki values to confirm the assumption that a drug with high affinity for the 5-HT uptake site would be hardly removed and have a long-lasting effect in vivo. Among the drugs tested, those with low Ki values, such as clomipramine, duloxetine and paroxetine, inhibited 5-HT uptake even after removal from the medium, while those with high Ki values such as amitriptyline, desipramine, imipramine, mianserin, trazodone, and zimelidine were easily removed by washing. The results indicated that low Ki values might be proportionally related to the long-lasting binding of drugs to the 5-HT uptake site. The results also suggested that the threshold Ki value which could separate 5-HT uptake inhibitors with a probable long-lasting effect in vivo from those without the effect would be between 5 nM and 42 nM.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9592808&dopt=Abstract

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Biol Psychiatry. 1998 May 15;43(10):774-80.
Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers.

Spigset O, Allard P, Mjorndal T.

Division of Clinical Pharmacology, Norrland University Hospital, Umea, Sweden.

BACKGROUND: Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS: Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). CONCLUSIONS: The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9606533&dopt=Abstract

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Neuroscience. 1998 Jul;85(1):63-72.
Intracerebral fetal raphe implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain.

Kelly PA, McBean DE, Ritchie IM.

Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, UK.

The effects of hypercapnia upon local cerebral blood flow and local cerebral glucose utilization were measured by quantitative autoradiography in parallel groups of rats (six per group) which 14-16 weeks previously had been treated with the serotonergic neurotoxin, methylenedioxymethamphetamine, followed by implantation of fetal raphe or basal forebrain tissues. Following the experiments, transplants were visualized by acetylcholinesterase histochemistry, and serotonergic reinnervation assessed using [3H]paroxetine binding to serotonin reuptake sites. In methylenedioxymethamphetamine-treated rats, contralateral to the implants, [3H]paroxetine binding was reduced by between 50 and 90% in the neocortex and hippocampus. Hippocampal glucose utilization was significantly increased in these rats, and the normal increase in flow which accompanies hypercapnia was also significantly enhanced. High levels of [3H]paroxetine binding were found within the raphe transplants (308 +/- 13 fmol/mg tissue). In host brain adjacent to the implant, binding levels were normalized, and in these same areas glucose utilization was also normalized. Basal forebrain implants had no effect upon either [3H]paroxetine binding or glucose utilization. Raphe transplants did not, however, alter the enhanced cerebrovascular response to hypercapnia induced by methylenedioxymethamphetamine, even in those areas where there was evidence of serotonergic reinnervation. The transplants also showed the same enhanced response. In conclusion, intracerebral fetal raphe implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain, and despite not sharing the serotonergic deficit, blood flow in the implants follows that of the dysfunctional host.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9607703&dopt=Abstract

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