Drugs online research references
Neuroreport. 1997 Nov 10;8(16):3571-5.
2'-Substitution of cocaine selectively enhances dopamine and norepinephrine transporter binding.
Seale TW, Avor K, Singh S, Hall N, Chan HM, Basmadjian GP.
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Few studies have characterized the effect of substituents at the 2'-position of cocaine on transporter binding potency and selectivity. We synthesized 2'-OH-, 2'-F- and 2'-acetoxy-cocaines and compared their binding potencies for rat dopamine, norepinephrine and 5-hydroxytryptamine transporters to cocaine, 3'-OH-, 4'-OH-, 2'-OH,4'-I-cocaine derivatives, and to the transporter selective ligands WIN 35,428, nisoxetine and paroxetine. Unlike most substitutions, 2'-OH- and 2'-acetoxy-groups increased cocaine's binding potency for the dopamine transporter (10- and 4-fold, respectively). These substituents also enhanced binding to the norepinephrine transporter (52- and 35-fold, respectively) but had less effect on 5-hydroxytryptamine transporter binding. 2'-Hydroxylation also enhanced binding of 4'-I cocaine, an analog with low DA binding potency. The ability of 2'-substituents to substantially increase cocaine binding potency and to alter selectivity for brain transporters indicates the potential importance of the 2'-position in transporter binding.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9427328&dopt=Abstract
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psychiatry.ox.ac.uk
We studied the effect of the selective serotonin reuptake inhibitor (SSRI), paroxetine, on basal plasma prolactin concentrations in 11 healthy subjects. Subjects were tested before paroxetine, and after 1 and 3 weeks of treatment (20 mg daily). On each test occasion prolactin levels were sampled before and following administration of a placebo capsule, for a total of 4 h. After 3 weeks paroxetine treatment plasma prolactin levels were significantly higher than those seen either pre-treatment or after 1 week of treatment. In contrast, 1 week of paroxetine treatment did not significantly increase prolactin concentrations over pre-treatment values. Plasma concentrations of paroxetine did not differ between 1 and 3 weeks of treatment. The secretion of plasma prolactin is, in part, under the tonic regulation of serotonergic pathways and the present results therefore support animal experimental data suggesting that SSRIs produce a delayed increase in some aspects of brain serotonin neurotransmission.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9443523&dopt=Abstract
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J Neural Transm. 1997;104(8-9):921-9.
High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains.
Rosel P, Arranz B, Vallejo J, Oros M, Menchon JM, Alvarez P, Navarro MA.
Hormone Unit (Biochemistry Department), Hospital Princeps D'Espanya, Barcelona, Spain.
Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides as compared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9451724&dopt=Abstract
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