Drugs online research references
Psychopharmacology (Berl). 1994 May;114(4):651-6.
Effects of (R)-alpha-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze.
Smith CP, Hunter AJ, Bennett GW.
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.
The effects of (R)-alpha-methylhistamine ((R)-alpha-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-alpha-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-alpha-MeHA and SCOP, (R)-alpha-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-alpha-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7855228&dopt=Abstract
Jpn J Pharmacol. 1995 May;68(1):85-94.
Involvement of raphe-hippocampal serotonergic and septo-hippocampal cholinergic mechanisms in the penile erection induced by FR121196, a putative cognitive enhancer.
Maeda N, Matsuoka N, Yamazaki M, Yamaguchi I.
Basic Research Group, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
FR121196 (N-[4-acetyl-1-piperazinyl]-4-fluorobenzenesulfonamide), a putative cognitive enhancer, induced penile erection in naive rats; the dose-response curve was bell-shaped with the maximum response obtained at the dose of 3.2 mg/kg. The response to FR121196 was abolished in rats treated with intra-raphe injections of 5,7-dihydroxytryptamine or systemic injections of p-chlorphenylalanine (150 mg/kg, i.p. for three consecutive days) as well as in rats with electrolytic medial-septum lesion or surgical fimbria-fornix lesion. In addition, the penile erection induced by FR121196 (3.2 mg/kg) was dose-dependently attenuated by pindolol (0.1-3.2 mg/kg), a serotonin (5-HT)1 antagonist with beta-antagonistic activity, but not by metoprolol, a selective beta=antagonist. The inhibitory activity was shared by ICS205-930, a 5-HT3 antagonist, but not by ketanserin, a 5-HT2 antagonist, or sulpiride, a dopamine D2 antagonist. Scopolamine (0.032-1 mg/kg), but not methyl-scopolamine (0.032-1 mg/kg), also attenuated the penile erection induced by FR121196. Neurochemical analysis revealed that intraperitoneal injection of FR121196 significantly elevated the levels of 5-HT and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and that raphe-lesion significantly reduced both 5-HT and 5-HIAA levels without affecting choline-acetyltransferase activity in all cortical and subcortical regions examined. It is thus postulated that FR121196 facilitates the raphe-hippocampal serotonergic pathway resulting in an activation of the septo-hippocampal cholinergic pathway and finally induces the penile erectile response.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7494387&dopt=Abstract
Naunyn Schmiedebergs Arch Pharmacol. 1987 Jun;335(6):605-12.
Muscarine receptors on the rat phrenic nerve, evidence for positive and negative muscarinic feedback mechanisms.
Wessler I, Karl M, Mai M, Diener A.
Neuronal transmitter stores of the rat phrenic nerve were labelled by incubation with [3H]choline. Release of [3H]acetylcholine was elicited by electrical nerve stimulation (100 or 1,500 pulses, 5 or 25 Hz) or by high potassium (27 mmol/l) and the effects of the muscarine receptor agonist oxotremorine and the antagonist scopolamine were investigated. Neither oxotremorine nor scopolamine affected the basal tritium efflux. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration of oxotremorine (1 mumol/l) reduced the electrically evoked [3H]acetylcholine release. Likewise, the high potassium-evoked [3H]acetylcholine release was reduced by a high concentration of oxotremorine. Both effects of oxotremorine, increase and decrease, were abolished by a pretreatment (30 min before the first stimulation period) with 0.1 mumol/l scopolamine. Scopolamine (0.1 mumol/l) alone, enhanced [3H]acetylcholine release evoked by 100 pulses (5 Hz) or by high potassium. Scopolamine, however, reduced [3H]acetylcholine release evoked by 1,500 pulses (5 Hz or 25 Hz). The concentration-response curves obtained for scopolamine under these latter stimulation conditions were flat-running and biphasic which might indicate the involvement of two opposite effects (increase and decrease) of scopolamine under the present stimulation conditions. Both effects of scopolamine were reduced in the presence of 10 mumol/l neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3627281&dopt=Abstract
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