Drugs online research references
Psychopharmacology (Berl). 1998 Nov;140(1):81-90.
Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not.
Fowler SC, Liou JR.
Department of Human Development, University of Kansas, Lawrence 66045, USA.
The purpose of this work was (1) to assess the ability of selected antipsychotic and comparison drugs to induce arrest of movement phenomena during operant responding and (2) to evaluate the capacity of muscarinic anitcholinergics to block such effects. The effects of haloperidol (0.02-0.12 mg/kg, i.p., 45 min), raclopride (0.05-0.80 mg/kg, i.p., 30 min) eticlopride (0.02-0.16 mg/kg, i.p., 45 min), clozapine (1.0-8.0 mg/kg, i.p., 60 min) and SCH 23390 (0.01-0.16 mg/kg, i.p., 30 min) were administered to rats for 4 weeks in a between-groups dosing design. Operant responses in 15 min and the maximum duration of the rat's muzzle entry into the reinforcement dipper well (the measure of arrest of movement that reflected microcatalepsy) were the quantitative measures of behavior. The D2 antagonists dose-relatedly decreased operant responding and increased maximum muzzle duration, effects that were significantly reversed by the anticholinergic scopolamine (0.1 mg/kg) or atropine (6.0 mg/kg). Although the atypical antipsychotic drug clozapine and the selective D1 antagonist SCH 23390 both significantly reduced operant responding, these drugs did not produce microcatalepsy. The results suggested that microcatalepsy expressed in the context of ongoing operant behavior may model low-dose extrapyramidal side effects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9862406&dopt=Abstract
J Pharmacol Exp Ther. 1999 Jan;288(1):164-70.
Selectivity profile of muscarinic toxin 3 in functional assays of cloned and native receptors.
Olianas MC, Ingianni A, Maullu C, Adem A, Karlsson E, Onali P.
Section on Biochemical Pharmacology, Departments of Neurosciences, University of Cagliari, Italy.
By using acetylcholine-induced stimulation of [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to membrane G proteins as a functional assay of the cloned human m1-m4 muscarinic receptor subtypes stably expressed in Chinese hamster ovary cells, muscarinic toxin 3 (MT3) was found to block the m4 receptor with a potency (pA2 = 8.33) much higher than those displayed at the m1 (pA2 = 6.78), m3 (pA2 = 6.3), and m2 (pA2 < 6.3) subtypes. In N1E-115 cells, which have been reported to express m4 receptors coupled to inhibition of cAMP, MT3 potently antagonized the carbachol-induced inhibition of adenylyl cyclase with a pA2 of 8. 81 and displayed monophasic inhibitory curves. Unexpectedly, in NG108-15 cells, known to express only m4 receptors, MT3 counteracted the carbachol inhibition of adenylyl cyclase with a lower potency (pA2 = 7.60) and showed a biphasic inhibitory curve, suggesting the participation of both m4 and m2 receptors. This possibility was supported by radioligand binding data showing that MT3 failed to completely displace the binding of [3H]N-methylscopolamine to NG108-15 cell membranes and by reverse transcription-polymerase chain reaction analysis, revealing the presence of mRNAs for both m4 and m2 receptor subtypes. These data demonstrate that MT3 possesses a high functional receptor selectivity for both the cloned and native m4 receptors and that in cell systems containing m4 and m2 receptors coupled to a common response, the toxin constitutes a powerful tool to resolve the relative contribution by each receptor subtype.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9862767&dopt=Abstract
J Pharmacol Exp Ther. 1999 Jan;288(1):302-15.
Novel 3alpha-diphenylmethoxytropane analogs: selective dopamine uptake inhibitors with behavioral effects distinct from those of cocaine.
Katz JL, Izenwasser S, Kline RH, Allen AC, Newman AH.
Psychobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
The pharmacological effects were assessed for a series of 3alpha-diphenylmethoxy-1alphaH,5alphaH-tropane analogs which have structural similarities to cocaine. Like cocaine, these compounds displaced [3H]WIN 35,428 binding from rat caudate and had affinities ranging from approximately 10-fold greater than cocaine (Ki=11.8 nM) to relatively low affinity (Ki=2000 nM). The compounds also inhibited dopamine uptake with potencies corresponding to their affinities for WIN 35,428 binding sites. Like the parent compound, benztropine, the 3alpha-(diphenylmethoxy)tropane analogs displaced [3H]pirenzepine from muscarinic M1 receptors with affinities ranging from 2 to 120 nM. Cocaine produced dose-related increases in locomotor activity (horizontal ambulation) in Swiss Webster mice, whereas the 3alpha-(diphenylmethoxy)tropane analogs generally had lower efficacy than cocaine. Compounds with fluoro-substituents in the phenyl rings generally were among those with efficacy approaching that of cocaine; those with chloro- and bromo-substituents were markedly less efficacious, despite having binding affinities comparable to those of the corresponding fluoro-substituted compounds. The 3alpha-(diphenylmethoxy)tropane analogs were also examined in rats trained to discriminate saline from cocaine (10 mg/kg, i.p.). Cocaine produced a dose-related increase in responding on the cocaine-appropriate lever, reaching 100% at 10 mg/kg. Only the 4',4"-difluoro-substituted analog produced effects similar to those of cocaine; the other compounds showed markedly reduced efficacy compared to cocaine. Drug interaction studies showed that the antimuscarinics, atropine and scopolamine, potentiated rather than attenuated the locomotor stimulant and cocaine-like discriminative-stimulus effects of cocaine, indicating that the antimuscarinic effects of the 3alpha-diphenylmethoxytropane analogs did not contribute to their diminished cocaine-like activity. Studies of the time course of selected compounds indicated that their reduced cocaine-like efficacy was likely not due to behavioral observations being conducted at an inopportune time period. Because none of the 3alpha-diphenylmethoxytropane analogs studied showed evidence that they were binding to more than one site, and because the structure activity relationships among these drugs are distinctly different from those obtained with cocaine, these data suggest that the 3alpha-diphenylmethoxytropane analogs are accessing a different binding domain than that accessed by cocaine. Binding to this domain may produce a behavioral profile that is distinct from that of the cocaine-like dopamine uptake inhibitors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9862785&dopt=Abstract
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Wellstreet online pharmacy for click-order prescription medications ||
Altace Online Pharmacy ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Insurance plans and information ||
Insurance policies for all purposes ||
Antibiotics and prescription medications online literature ||