In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro.

Abstract:

:Lu 25-109 [5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1-methylpyridine] , has M agonistic and M2/M3 antagonistic effects at muscarinic receptors in vitro; a pharmacological profile that may be beneficial in treatment of Alzheimer's disease. In the present study, we compare functional in vivo effects of Lu 25-109 and reference compounds in animal models of muscarinic cholinergic function. Lu 25-109 substituted completely for the discriminative stimulus effects of (-)-7-methyl-3-(2-propynyloxy)-4,5,6,7-tetrahydroisothiazolo -[4, 5-c]pyridine (Lu 26-046), a partial M1/M2 agonist, but only weakly for the effects of the non-selective M1/M2/M3 agonist 3-methoxy-4,5,6,7-tetrahydro-isoxazolo[4, 5-c] pyridine (O-Me-THPO). Lu 25-109 did not reverse O-Me-THPO-induced discriminative stimulus. Tacrine did not substitute for any of the training drugs. Lu 25-109 did not substitute in (-)-nicotine trained rats. Lu 25-109 did not antagonize oxotremorine-induced hypothermia, tremor and salivation in mice and antagonized physostigmine-induced lethality with low potency. Unlike non-selective muscarinic agonists and acetylcholinesterase inhibitors, Lu 25-109 did not induce hypothermia, tremor or salivation in mice. Spontaneous locomotor activity and motor co-ordination were inhibited only at high doses. Lu 25-109 had no effect on mean blood pressure in anaesthetized rats. Lu 25-109 and O-Me-THPO produced a significant increase in heart rate. The maximum increase was 37%. In anaesthetized cats, increasing i.v. doses of Lu 25-109 were without effect on the mean blood pressure, except for a short lasting (<2 min) depressor effect following the IV injection. Furthermore, Lu 25-109 did not attenuate the reflex mechanisms restoring blood pressure following orthostasis in cats. In conclusion, the drug discrimination studies suggest a unique activity profile of Lu 25-109, and the in vivo profile suggests none or a very low frequency of unwanted cholinergic mediated effects.

journal_title

Psychopharmacology

authors

Sánchez C,Arnt J,Didriksen M,Dragsted N,Moltzen Lenz S,Matz J

doi

10.1007/s002130050615

subject

Has Abstract

pub_date

1998-06-01 00:00:00

pages

233-40

issue

3

eissn

0033-3158

issn

1432-2072

journal_volume

137

pub_type

杂志文章
  • A new method for the evaluation of benzodiazepines based on their ability to block muscimol-induced myoclonic jerks in mice.

    abstract::A number of clinically used benzodiazepines were tested for their effectiveness in blocking muscimol-induced myoclonic jerks in mice. Their ED50 values were determined from their dose-response curves. These data gave the following relative potencies with respect to diazepam: diazepam = 1, medazepam = 0.24, oxazepam = ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00432441

    authors: Menon MK,Vivonia CA,Haddox VG

    更新日期:1981-01-01 00:00:00

  • The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration.

    abstract:RATIONALE:Buprenorphine reduces both heroin and cocaine intake in opioid addicts, but the mechanisms remain unclear. OBJECTIVES:To determine the effects of chronic buprenorphine treatment on intake of heroin and/or cocaine and measure nucleus accumbens (NAc) dopamine (DA) levels during self-administration. METHODS:In...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-006-0485-1

    authors: Sorge RE,Stewart J

    更新日期:2006-09-01 00:00:00

  • Dorsal-striatal 5-HT₂A and 5-HT₂C receptors control impulsivity and perseverative responding in the 5-choice serial reaction time task.

    abstract:RATIONAL:Prefrontal cortex (PFC) and dorsal striatum are part of the neural circuit critical for executive attention. The relationship between 5-HT and aspects of attention and executive control is complex depending on experimental conditions and the level of activation of different 5-HT receptors within the nuclei of ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-011-2581-0

    authors: Agnoli L,Carli M

    更新日期:2012-01-01 00:00:00

  • The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

    abstract:RATIONALE:Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. OBJECTIVE:The present study assesses...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-014-3658-3

    authors: Carbonaro TM,Eshleman AJ,Forster MJ,Cheng K,Rice KC,Gatch MB

    更新日期:2015-01-01 00:00:00

  • Instinctive predatory behavior of the ferret (Putorius putorius furo L.) modified by chlordiazepoxide hydrochloride (Librium).

    abstract::The predatory behavior of ferrets (Putorius putorius furo L.) consists mainly of instinctive behavioral patterns that are elicited by simple external stimuli. For the ferret, the time needed to catch and kill rats depends on the size of the rats in relation to that of the ferret. Killing success decreases with a relat...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00427754

    authors: Apfelbach R

    更新日期:1978-10-31 00:00:00

  • Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats.

    abstract:RATIONALE:Like other monoamine releasers such as D-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys. OBJECTIVES:The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse. METHODS:In expe...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-015-3875-4

    authors: Czoty PW,Tran P,Thomas LN,Martin TJ,Grigg A,Blough BE,Beveridge TJ

    更新日期:2015-07-01 00:00:00

  • Erythrocyte glycine in depressed, hypomanic, and euthymic bipolar patients treated with lithium carbonate.

    abstract::Red blood cell (RBC) glycine levels were examined in 27 bipolar patients, treated with lithium carbonate for a minimum of 8 months, who were either hypomanic, depressed, or euthymic in their mood. We found no difference in the RBC glycine or in the RBC: plasma glycine ratio between the hypomanic, depressed, or euthymi...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00433732

    authors: Peselow ED,Deutsch SI,Stanley M,Banay-Schwartz M,Virgilio J,Fieve RR

    更新日期:1982-01-01 00:00:00

  • Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways.

    abstract:RATIONALE AND OBJECTIVES:Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00213-016-4235-8

    authors: Krasnova IN,Justinova Z,Cadet JL

    更新日期:2016-05-01 00:00:00

  • Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity.

    abstract::Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02180028

    authors: Marco LA,Joshi RS,Brown C,Aldes LD,Chronister RB

    更新日期:1988-01-01 00:00:00

  • Differential effect of benzodiazepine sedation in high and low anxious patients in a "real life" stress setting.

    abstract::In a randomised, double-blind, parallel groups study, 40 patients referred for surgical removal of impacted third molars received either (a) temazepam 40 mg orally followed at 35 min by IV saline or (b) oral placebo followed by IV diazepam 10 mg (Diazemuls). Patients were divided into High-Anxious and Low-Anxious grou...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00652245

    authors: O'Boyte CA,Harris D,Barry H,Cullen JH

    更新日期:1986-01-01 00:00:00

  • Development and loss of tolerance to morphine in the rat.

    abstract::The development of a differential tolerance to morphine was investigated with respect to the mean effective dose, the threshold dose of tolerance, the degree of tolerance after a fixed dose, and the speed of tolerance loss. The mean effective doses, the threshold doses of tolerance, and the degree of tolerance differe...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00428157

    authors: Fernandes M,Kluwe S,Coper H

    更新日期:1982-01-01 00:00:00

  • The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice.

    abstract:RATIONALE:Neuropeptide Y (NPY) is implicated in the pathophysiology of affective illness. Multiple receptor subtypes (Y1R, Y2R, and Y5R) have been suggested to contribute to NPY's effects on rodent anxiety and depression-related behaviors. OBJECTIVES:To further elucidate the role of Y1R in (1) NPY's anxiolytic-like ef...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-007-0945-2

    authors: Karlsson RM,Choe JS,Cameron HA,Thorsell A,Crawley JN,Holmes A,Heilig M

    更新日期:2008-01-01 00:00:00

  • Context, acute tolerance, and subjective response affect alcohol-impaired driving decisions.

    abstract:RATIONALE:Alcohol intoxication produces effects that can impair judgment and increase engagement in risky behaviors, including alcohol-impaired driving (AID). Real-world AID decisions are informed by contextual circumstances and judgments of associated risk. How individuals vary in their AID decision-making across cont...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-020-05639-0

    authors: Motschman CA,Warner OM,Wycoff AM,Davis-Stober CP,McCarthy DM

    更新日期:2020-12-01 00:00:00

  • Acute effects of a short bout of moderate versus light intensity exercise versus inactivity on tobacco withdrawal symptoms in sedentary smokers.

    abstract:RATIONALE:A previous study found that a 10-min bout of moderate intensity exercise reduced cigarette withdrawal symptoms and desire to smoke in sedentary smokers but the effect may have been due to participants focusing attention on physical activity rather than the activity itself. OBJECTIVES:This study examined the ...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/s00213-003-1762-x

    authors: Daniel J,Cropley M,Ussher M,West R

    更新日期:2004-07-01 00:00:00

  • Effects of single and long-term haloperidol administration on open field behavior of rats.

    abstract::The effects of single and long-term haloperidol administration on rat open field behavior was studied. Withdrawal from long-term haloperidol treatment induced a significant increase in all parameters of activity recorded, except rearing. There was a direct relationship between the impairment of motor function induced ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00429212

    authors: Bernardi MM,De Souza H,Palermo Neto J

    更新日期:1981-01-01 00:00:00

  • Tobacco smoke containing high or low levels of nicotine during adolescence: effects on novelty-seeking and anxiety-like behaviors in mice.

    abstract:RATIONALE:Thousands of adolescents start smoking daily but information on the effects of tobacco exposure on this age group is scarce. Moreover, the available animal models rely on the effects of nicotine, neglecting other neuroactive components of tobacco. OBJECTIVES:We investigated the effects of exposure of adolesc...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-014-3801-1

    authors: Abreu-Villaça Y,Filgueiras CC,Correa-Santos M,Cavina CC,Naiff VF,Krahe TE,Manhães AC,Ribeiro-Carvalho A

    更新日期:2015-05-01 00:00:00

  • Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine.

    abstract::The pharmacokinetic and pharmacodynamic effects of concomitant administration of alprazolam and fluoxetine were studied in this double-blind parallel study in 80 healthy, male volunteers. Subjects were randomly assigned to one of four treatment groups. Drug treatments consisted of 4-day regimens of 1 mg alprazolam fou...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF02246031

    authors: Lasher TA,Fleishaker JC,Steenwyk RC,Antal EJ

    更新日期:1991-01-01 00:00:00

  • NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors.

    abstract::NCQ 298 ((S)-3-iodo-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide) has an iodine substituent. We have labelled NCQ 298 with 123I and 125I, and used the radioligands as tracers in receptor studies in vitro, in vivo in autoradiography and in SPECT studies on Cynomolgus monkeys. [125I]NCQ 298 bound in vit...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02244067

    authors: Hall H,Högberg T,Halldin C,Köhler C,Ström P,Ross SB,Larsson SA,Farde L

    更新日期:1991-01-01 00:00:00

  • Treatment of Schizophrenia with ergot derivatives.

    abstract::Seven neuroleptic-free schizophrenic patients received bromocriptine and eight schizophrenic patients received CF 25-397, both ergot derivatives with dopamine agonist activity. Psychosis failed to improve in response to either drug at the relatively low doses administered. Unlike the antipsychotic property of apomorph...

    journal_title:Psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00428312

    authors: Tamminga CA,Schaffer MH

    更新日期:1979-01-01 00:00:00

  • The ascending limb of the cocaine dose-response curve for reinforcing effect in rhesus monkeys.

    abstract:RATIONALE:To date, the literature on the intravenous self-administration of cocaine by laboratory animals lacks a compelling demonstration of an ascending limb to the dose-response function. It has been argued that previous demonstrations of an ascending limb are confounded by the extinction process. OBJECTIVE:The obj...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-002-1336-3

    authors: Flory GS,Woods JH

    更新日期:2003-02-01 00:00:00

  • Electrolytic lesions and pharmacological inhibition of the dorsal raphe nucleus prevent stressor potentiation of morphine conditioned place preference in rats.

    abstract:RATIONALE:Exposure to a single session of uncontrollable inescapable shock (IS), but not to identical controllable escapable shock, produces a potentiation of morphine's rewarding properties that is unusual in that the stressor can be given a number of days before the drug administration in an environment quite differe...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-003-1572-1

    authors: Will MJ,Der-Avakian A,Bland ST,Grahn RE,Hammack SE,Sparks PD,Pepin JL,Watkins LR,Maier SF

    更新日期:2004-01-01 00:00:00

  • Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats.

    abstract:RATIONALE:Acute physical dependence refers to the withdrawal syndrome precipitated by an opioid antagonist administered several hours after either a single dose or a short-term infusion of an opioid agonist. OBJECTIVES:We examined the mechanism of nicotine-induced attenuation of naloxone-precipitated withdrawal syndro...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-003-1595-7

    authors: Araki H,Kawakami KY,Jin C,Suemaru K,Kitamura Y,Nagata M,Futagami K,Shibata K,Kawasaki H,Gomita Y

    更新日期:2004-02-01 00:00:00

  • Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels.

    abstract:RATIONALE:Serotonin (5-HT) plays a key role in different aspects of value-based decision-making. A recent framework proposed that tonic 5-HT (together with dopamine, DA) codes future average reward expectations, providing a baseline against which possible choice outcomes are compared to guide decision-making. OBJECTIV...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-018-4913-9

    authors: Neukam PT,Kroemer NB,Deza Araujo YI,Hellrung L,Pooseh S,Rietschel M,Witt SH,Schwarzenbolz U,Henle T,Smolka MN

    更新日期:2018-07-01 00:00:00

  • Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on kappa-opioid agonists in the mouse writhing assay.

    abstract::The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02245071

    authors: Broadbear JH,Negus SS,Butelman ER,de Costa BR,Woods JH

    更新日期:1994-07-01 00:00:00

  • Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress.

    abstract:RATIONALE:Severe, traumatic stress or repeated exposure to stress can result in long-term deleterious effects, including hippocampal cell atrophy and death, which, in turn, result in memory impairments and behavioural abnormalities. The dopaminergic D(2) receptor agonist, bromocriptine, has been shown to modulate learn...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-007-0801-4

    authors: Srikumar BN,Raju TR,Shankaranarayana Rao BS

    更新日期:2007-08-01 00:00:00

  • Retarded acquisition and reduced expression of conditioned locomotor activity in adult rats following repeated early maternal separation: effects of prefeeding, d-amphetamine, dopamine antagonists and clonidine.

    abstract::Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the r...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02246414

    authors: Matthews K,Hall FS,Wilkinson LS,Robbins TW

    更新日期:1996-07-01 00:00:00

  • Cocaine enhances memory storage in mice.

    abstract::Mice were trained on a one-trial inhibitory avoidance task and given immediate post-training intraperitoneal injections of cocaine (0.03-1.00 mg/kg). On a retention test 24 h later, the retention latencies of mice given the 0.10 mg/kg dose were significantly higher than those of the controls. The effect of cocaine on ...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00589905

    authors: Introini-Collison IB,McGaugh JL

    更新日期:1989-01-01 00:00:00

  • Genetic deletion of dopamine D1 receptors increases the sensitivity to cannabinoid CB1 receptor antagonist-precipitated withdrawal when compared with wild-type littermates: studies in female mice repeatedly exposed to the Spice cannabinoid HU-210.

    abstract:RATIONALE:The emergence of the consumption of highly potent synthetic cannabinoid receptor agonists (spice drugs) that produce important neurological symptoms has prompted the research on the consequences of acute and chronic use of these new psychoactive substances. Most studies on cannabinoid dependence have been per...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-020-05704-8

    authors: Serrano A,Vadas E,Ferrer B,Bilbao A,Granado N,Suárez J,Pavon FJ,Moratalla R,Rodríguez de Fonseca F

    更新日期:2021-02-01 00:00:00

  • Pharmacological specificity of enhanced sensitivity to naltrexone in rats.

    abstract::Rats treated weekly with cumulative doses (1-100 mg/kg, IP) of naltrexone develop an enhanced sensitivity to the operant response-rate decreasing effect of naltrexone. In the present experiment the pharmacological specificity of that enhanced sensitivity was determined by testing a variety of drugs for cross-sensitivi...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02246951

    authors: Schindler CW,Goldberg SR,Katz JL

    更新日期:1993-01-01 00:00:00

  • Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice.

    abstract:INTRODUCTION:Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be use...

    journal_title:Psychopharmacology

    pub_type: 杂志文章

    doi:10.1007/s00213-020-05522-y

    authors: Chen L,Pan H,Bai Y,Li H,Yang W,Lin ZX,Cui W,Xian YF

    更新日期:2020-07-01 00:00:00