Drugs online research references
Eur J Pharmacol. 1979 Mar 15;54(4):331-9.
Dopamine--acetylcholine "balance" in nucleus accumbens and corpus striatum and its effect on hypothalamic self-stimulation.
Stephens DN, Herberg LJ.
Three experiments investigated the suppression of hypothalamic self-stimulation in rats by neuroleptics and its restoration by centrally acting anticholinergic agents. Scopolamine (0.1--1.0 mg/kg i.p.) and benztropine (1.0--10.0 mg/kg i.p.) each enhanced self-stimulation when administered alone, and partially restored performance suppressed by spiroperidol (0.05--0.15 mg/kg i.p.). Benztropine strongly inhibits transmitter reuptake at DA synapses but scopolamine does not, thus inhibition of DA reuptake cannot fully account for the stimulant or antineuroleptic action of anticholinergic drugs. Neuroleptic and anticholinergic effects on self-stimulation rate were mutually subtractive, and statistical evidence of interaction was not obtained. Scopolamine was shown also to restore performance extinguished by discontinuation of the stimulating current. Smaller doses of scopolamine (50 nmol; 19 microgram) injected directly into the nucleus accumbens septi partially restored responding suppressed by spiroperidol, though similar doses of scopolamine injected bilaterally into the caudate-putamen were ineffective. These findings suggest that hypothalamic self-stimulation may be influenced by ACh-and DA-containing systems which exert independent effects on a third system controlling performance. These effects appear to reflect the level of arousal or motivation rather than the reinforcement process itself.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=436932&dopt=Abstract
Psychopharmacology (Berl). 1990;101(3):371-5.
Effect of imipramine in the "learned helplessness" model of depression in rats is not mimicked by combinations of specific reuptake inhibitors and scopolamine.
Geoffroy M, Scheel-Kruger J, Christensen AV.
Psychopharmacological Research Laboratory, St. Hans Hospital, Roskilde, Denmark.
Administration of imipramine, which blocks noradrenergic, serotonergic and cholinergic reuptake, to rats for 4 days counteracts the shuttlebox escape failures otherwise seen in rats which have been exposed to inescapable shock (the "learned helplessness" model of depression). The effects of the more selective reuptake inhibitors talsupram (noradrenergic), citalopram (serotonergic) and the anticholinergic compound scopolamine were assessed alone and in combination after acute or 4 days' administration on escape behavior. Their possible synergistic effects when combined with imipramine were also assessed. Talsupram and citalopram were ineffective, whereas scopolamine counteracted the escape failures. Combinations of talsupram, citalopram and a subeffective dose of scopolamine were ineffective. A synergistic effect was only seen when scopolamine was combined with a suboptimal dose of imipramine. Thus, the effect of imipramine on "learned helplessness" might rely partly on its anticholinergic component. However, as an acute high dose of imipramine (25 mg/kg) was ineffective [unlike the acute administration of scopolamine (0.12 mg/kg)], this drug retains a pharmacological effect which is not mimicked by scopolamine alone or by combining the specific reuptake inhibitors with scopolamine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2141946&dopt=Abstract
J Med Chem. 1990 Feb;33(2):741-8.
Functionalized congener approach for the design of novel muscarinic agents. Synthesis and pharmacological evaluation of N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl] amides.
Bradbury BJ, Baumgold J, Jacobson KA.
Laboratory of Chemistry, NIDDK, National Institute of Health, Bethesda, Maryland 20892.
A functionalized congener approach was used to design ligands for muscarinic cholinergic receptors (mAChRs). A series of omega-functionalized alkyl amides of N-methyl-4-(1-pyrrolidinyl)-2-butynamine (22) were prepared as functionalized analogues of UH 5 [N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl]acetamide], a muscarinic agonist related to oxotremorine. Intermediate 22 was coupled to a series of Boc-protected omega-amino acids, and the resulting amides were deprotected and acylated. Intermediate 22 was also acylated with succinic anhydride and derivatized. The synthetic intermediates and final compounds were evaluated in vitro for their effects on the turnover of phosphatidylinositides in SK-N-SH human neuroblastoma cells that express m3AChRs, and on the production of cyclic AMP in NG108-15 neuroblastoma x glioma cells that express only m4AChRs. The displacement of [3H]-N-methylscopolamine was also measured in membrane preparations from each of these cell lines. Conjugates of glycine and beta-alanine were agonists at m4AChRs, having little or no activity at m3AChRs. The potency in displacement of [3H]-N-methylscopolamine from both m3- and m4AChRs generally increased with increasing chain lengths of the omega-aminoalkyl congeners. The amides of 7-aminoheptanoic acid and 8-aminooctanoic acid, and their Boc-protected derivatives, had comparable affinities to UH 5 (Ki = 5.0 and 4.5 microM at m3AChRs and at m4AChRs, respectively) at both receptors but lacked any agonist effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2153827&dopt=Abstract
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