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_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Sánchez C,Arnt J,Didriksen M,Dragsted N,Moltzen Lenz S,Matz Jdoi
10.1007/s002130050615subject
Has Abstractpub_date
1998-06-01 00:00:00pages
233-40issue
3eissn
0033-3158issn
1432-2072journal_volume
137pub_type
杂志文章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
更新日期:1981-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00213-014-3658-3
更新日期:2015-01-01 00:00:00
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pub_type: 杂志文章
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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...
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pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章,随机对照试验
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doi:10.1007/s00213-007-0945-2
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3801-1
更新日期:2015-05-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02246031
更新日期:1991-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-02-01 00:00:00
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更新日期:2004-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-003-1595-7
更新日期:2004-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245071
更新日期:1994-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-007-0801-4
更新日期:2007-08-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246414
更新日期:1996-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00589905
更新日期:1989-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05704-8
更新日期:2021-02-01 00:00:00
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
更新日期:1993-01-01 00:00:00
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
更新日期:2020-07-01 00:00:00