Drugs online research references









J Psychopharmacol. 1997;11(1):53-8.
Behavioural effects of selective serotonin reuptake inhibitors following direct micro injection into the left red nucleus of the rat.

Faherty CJ, Earley B, Leonard BE.

Department of Pharmacology, University College, Galway, Ireland.

The behavioural effects of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram, fluvoxamine, fluoxetine) and reference compounds (N,N'-di(o-tolyl)guanidine, haloperidol, 3-(3-hydroxyphenyl)-N-(l-propyl)piperidine and chlorpromazine) were studied for their ability to produce dystonia and torticollis following direct micro injection into the left red nucleus of the rat, an area of the brain containing a high density of sigma2 receptors but relatively devoid of biogenic amine receptors. Each animal was monitored for abnormalities in posture and movement for a period of 30 min and then sacrificed 40 min following drug administation. Only fluvoxamine (100 nmol) and fluoxetine (100 nmol) elicited acute dystonic behaviour (1-5 min). The onset of dystonia was accompanied by facial spasticity, vacuous chewing movements and grooming behaviour which reflected the extent of dystonia. The dystonic behaviour following the direct intrarubal injection of fluvoxamine and fluoxetine suggest the possible activation of sigma2 receptors while citalopram, sertraline and paroxetine were without effect. The results of this study support the role of sigma2 receptors in the regulation and control of movement and coordination and provides preliminary evidence to suggest the in vivo activity of sigma receptors by fluoxetine and fluvoxamine.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9097894&dopt=Abstract

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Br J Pharmacol. 1997 Apr;120(7):1255-62.
An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine.

Meoni P, Tortella FC, Bowery NG.

Department of Pharmacology, School of Pharmacy, University of London.

1. The distribution and some pharmacological properties of centrally located dextromethorphan high-affinity binding sites were investigated by in vitro autoradiography. 2. Sodium chloride (50 mM) induced a 7 to 12 fold increase in dextromethorphan binding to rat brain in all areas tested. The effect of sodium was concentration-dependent with a higher dose (120 mM) exerting a smaller effect on binding. 3. [3H]-dextromethorphan binding in the presence of sodium was inhibited in the presence of the anticonvulsant phenytoin at a concentration of 100 microM, while the sigma ligand (+)-3-(-3-hydroxyphenyl)-N-(1-propyl)pipendine ((+)-PPP) had no effect on the binding, suggesting an interaction with the DM2 site. 4. The distribution of the sodium-dependent binding identified in this study correlated significantly with the distribution of the selective 5-HT uptake inhibitor [3H]-paroxetine, and paroxetine and dextromethorphan mutually displaced their binding at concentrations in the low nanomolar range. 5. These data show that dextromethorphan and paroxetine share a sodium-dependent high affinity binding site in rat brain, and suggest that dextromethorphan might interact, in the presence of sodium, with the 5-HT uptake mechanism in rat brain.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9105700&dopt=Abstract

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Pol J Pharmacol. 1996 Nov-Dec;48(6):565-73.
Antidepressant-induced adaptive changes in the effects of 5-HT, 5-HT1A and 5-HT4 agonists on the population spike recorded in hippocampal CA1 cells do not involve presynaptic effects on excitatory synaptic transmission.

Tokarski K, Bijak M.

Department of Neurobiology, Polish Academy of Sciences, Krakow, Poland.

Effects of repeated treatment with antidepressant drugs on the reactivity of CA1 neurons to 5-hydroxytryptamine (5-HT), (+/-)-8-hydroxy-2-(dipropyl-amino)-tetralin (8-OH-DPAT)--the 5-HT1A receptor agonist, and the zacopride-5-HT4 receptor agonist were examined in the rat hippocampus ex vivo. We sought to assess whether a presynaptic action of 5-HT receptor agonists on excitatory synaptic transmission contributed to the antidepressant-induced adaptive changes in responsiveness of pyramidal neurons to 5-HT1A and 5-HT4 receptor activation. The dendritic population excitatory postsynaptic potential (EPSP) evoked in the stratum radiatum of the CA1 region by stimulation of the Schaffer collateral-commissural pathway, was employed as a measure of the excitatory amino acid-mediated synaptic transmission, while the population spike recorded simultaneously in the CA1 cell layer was a measure of pyramidal cell excitability. 5-HT (10 microM) and 8-OH-DPAT (1 microM) decreased (by 40 +/- 5% and 30 +/- 7%, respectively), while zacopride (20 microM) increased (by 50 +/- 8%) the amplitude of the population spike. Neither drug had any effect on the slope of the population EPSP. The selective 5-HT1B receptor agonist CGS-12066 had no effect on the population spike or on the EPSP. Repeated treatment (14 days, twice daily, 10 mg/kg po) with imipramine and paroxetine augmented the inhibitory action of 5-HT on the population spike (by 50%), whereas treatment with citalopram and fluvoxamine had no effect. Imipramine and paroxetine, but not fluvoxamine, increased the 8-OH-DPAT-induced inhibition (by 80-100%). All of the antidepressant drugs studied attenuated the excitatory effect of zacopride on the population spike (by 70%). The population EPSPs in slices from rats treated with antidepressant drugs were not affected by 5-HT, 8-OH-DPAT or zacopride. It has been concluded that adaptive changes in the responsiveness of CA1 cells to 5-HT, 8-OH-DPAT and zacopride, induced by repeated administration of antidepressant drugs do not involve presynaptic effects on excitatory synaptic transmission.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9112695&dopt=Abstract

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