Drugs online research references
Eur J Pharmacol. 1994 Nov 3;264(3):241-7.
Isolation-induced aggression in mice: effects of 5-hydroxytryptamine uptake inhibitors and involvement of postsynaptic 5-HT1A receptors.
Sanchez C, Hyttel J.
H. Lundbeck A/S, Copenhagen-Valby, Denmark.
The inhibitory potencies of selective serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitors on isolation-induced aggressive behaviour in male mice were studied. Furthermore, the role of postsynaptic 5-HT1A receptors in the mediation of aggressive behaviour was studied. The selective 5-HT uptake inhibitors, sertraline, floxetine, femoxetine and fluvoxamine, showed weak antiaggressive effects, and citalopram and paroxetine were ineffective. This rank of potencies corresponded with neither uptake inhibitory potencies in vitro nor potentiation of 1-5-hydroxytryptophan (1,5-HTP)-induced motor effects in vivo, as citalopram and paroxetine were among the most potent compounds in these tests. A subeffective dose of 1,5-HTP (110 mumol/kg = 25 mg/kg, s.c.) potentiated the antiaggressive effect of citalopram and paroxetine more than 110 and 1600 times, respectively. The effects of sertraline, fluvoxamine, fluoxetine and femoxetine were only potentiated 3, 36, 4 and 16 times, respectively. The 5-HT releasing compound fenfluramine inhibited the aggressive behaviour dose dependently, and depletion of 5-HT by treatment with p-chloro-phenylalanine methyl ester attenuated this effect significantly. p-Chloro-phenylalanine methyl ester was ineffective itself, but potentiated the antiaggressive effect of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamin)tetralin (8-OH-DPAT). The beta-adrenoceptor/5-HT1A receptor antagonist, (-)-penbutolol, reversed the antiaggressive effects of 8-OHDPAT. In conclusion, selective 5-HT uptake inhibitors act in different ways on isolation-induced aggressive behaviour, and postsynaptic 5-HT1A receptors are involved in mediating the aggressive behaviour.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7698161&dopt=Abstract
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Eur J Pharmacol. 1994 Dec 27;271(2-3):461-9.
The effects of sertraline on nicotine self-administration and food-maintained responding in squirrel monkeys.
Sannerud CA, Prada J, Goldberg DM, Goldberg SR.
Behavioral Pharmacology and Genetics Section, NIDA-Intramural Research Program, Baltimore, MD 21224.
Recent reports suggested the involvement of serotonergic mechanisms in nicotine self-administration. The present study assessed the effects of sertraline, a selective serotonergic uptake inhibitor, on the reinforcing effects of i.v. nicotine (30 microgram/kg per injection) in squirrel monkeys responding under a fixed-ratio schedule. Nicotine (10-100 micrograms/kg per injection) produced a significant inverted U-shaped distribution on FR rate. Vehicle or sertraline (3, 6, 12, 24 mg/kg, p.o.) produced no changes in the response rates maintained by 30 micrograms/kg per injection i.v. nicotine, but sertraline produced non-significant increases response rates maintained by 10 micrograms/kg per injection nicotine and vehicle. In a separate group of monkeys, sertraline given in combination with i.m. doses of nicotine produced a significant dose-dependent decrease in responding maintained by food-pellet delivery. Thus, sertraline produced differential effects on response rates that may be related to (1) route of nicotine administration and (2) whether the behavior was maintained by nicotine or food. In addition, the results of the self-administration study suggest that sertraline would not disrupt well-maintained responding for nicotine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7705446&dopt=Abstract
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Eur J Pharmacol. 1995 Feb 15;288(3):373-7.
Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets.
Helmeste DM, Tang SW, Reist C, Vu R.
Department of Psychiatry, Veterans Administration Medical Center, Long Beach, CA 90822, USA.
The serotonin uptake inhibitors sertraline, paroxetine and fluoxetine were compared with imipramine and the calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7) and calmidazolium, for their effects on intracellular Ca2+ mobilization in human platelets. All serotonin uptake inhibitors and calmodulin antagonists augmented thrombin-mediated increases in intracellular Ca2+. Sertraline, calmidazolium and W-7 also caused large dose-dependent increases in baseline levels of intracellular Ca2+. There was a rough correlation between the ability to elevate intracellular Ca2+ and potencies for inhibition of calmodulin. Neomycin, an inhibitor of inositol trisphosphate (IP3) generation, significantly inhibited the effects of sertaline. This is consistent with a role of IP3 and calmodulin in the effects of these drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7774682&dopt=Abstract
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