Abstract：
:The new antisecretory drug, telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno-[3,4 - b][1,5]benzodiazepin-10-one), was investigated for its inhibition of functionally intact muscarinic receptors involved in gastric acid secretion in rabbit fundic glands, perfused mouse stomach in vitro, perfused rat stomach in situ, gastric fistula in rats and dogs with a Heidenhain pouch. The effects on these receptors were contrasted with effects on receptors located on smooth muscle and heart, i.e. isolated rat urinary bladder, stomach and atrium. The results were compared to those values obtained with nonselective antimuscarinic drugs (N-methylscopolamine, atropine) and the selective M-1 antagonist pirenzepine. Telenzepine was found to be 4-10 times more potent than pirenzepine with respect to depressing both gastric acid secretion and smooth muscle or myocardial responses. Based on -log EC50 and pA2 values, both drugs exhibited a similar selectivity profile differing from the pattern of effects observed with atropine or a second reference compound, zolenzepine. As compared with atropine, telenzepine exhibited a 5 fold higher relative affinity to muscarinic receptors involved in gastric acid secretion. It was concluded that telenzepine is selective to discriminate between muscarinic receptors mediating gastric acid secretion and affecting muscle contractility and that this finding supports the concept of muscarinic receptor heterogeneity.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Eltze M,Gönne S,Riedel R,Schlotke B,Schudt C,Simon WAdoi
10.1016/0014-2999(85)90498-4subject
Has Abstractpub_date
1985-06-07 00:00:00pages
211-24issue
2eissn
0014-2999issn
1879-0712pii
0014-2999(85)90498-4journal_volume
112pub_type
杂志文章abstract：:Endothelins, 21-amino acid peptides involved in the pathogenesis of various diseases, bind to endothelin ET(A) and ET(B) receptors to initiate their effects. Here, we characterize the pharmacology of A-216546 ([2S-(2,2-dimethylpentyl)-4S-(7-methoxy-1,3-benzodioxol-5-yl )-1-(N,N-di(n-butyl) aminocarbonylmethyl)-pyrroli...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00891-7
更新日期：1999-02-05 00:00:00
abstract：:Clonidine reduced cardiac acceleration induced by low frequency electrical stimulation of cardiac sympathetic nerve fibers in anesthetized and vagotomized dogs. This effect of clonidine was abolished by short periods of high frequency electrical stimulation. The inhibitory effect of clonidine was observed with 10- as ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90191-1
更新日期：1977-03-07 00:00:00
abstract：:Multiple myeloma is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in multiple myeloma. Histone lysine methylation has emerged as a central epigenetic change in the organization of eukaryotic chromatin with far-reaching implications for the re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.05.034
更新日期：2010-11-10 00:00:00
abstract：:We report that certain substituted hexahydrobenzo[a]phenanthridines are novel high affinity ligands selective for the dopamine D3 receptor. These data demonstrate that substitutions on the heterocyclic nitrogen and the pendant phenyl ring of this nucleus cause a marked increase in both affinity and selectivity for dop...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)91012-c
更新日期：1993-08-03 00:00:00
abstract：:Dinitrosyl iron complexes (DNIC) with glutathione exert a cytotoxic effect on endometrioid tumours in rats with surgically induced experimental endometriosis. Intraperitoneal treatment of rats (Group 1) with DNIC (12.5μmoles/kg, daily, for 12 days), beginning with day 4 after the surgical operation (implantation of tw...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.002
更新日期：2014-03-15 00:00:00
abstract：:Studies have demonstrated that long-term opioid treatment leads to an increased sensitivity to painful (hyperalgesia) or normally innocuous (allodynia) stimuli. The molecular mechanisms that lead to paradoxical pain sensitization upon chronic opioid treatment are not completely understood. Enhanced excitatory pain neu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.10.033
更新日期：2008-12-28 00:00:00
abstract：:We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we fur...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.03.023
更新日期：2012-05-15 00:00:00
abstract：:The beta-carboline FG7142 is a partial inverse agonist at benzodiazepine receptors. We have shown previously that a single dose of this drug causes an upregulation of cortical beta-adrenoceptor numbers in mouse cerebral cortex. This rise was seen seven days, but not 15-30 min or 24 h after FG7142 administration. We no...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90255-x
更新日期：1987-07-09 00:00:00
abstract：:gamma-Aminobutyric acid B (GABA(B)) receptor is the first discovered G protein-coupled receptor that requires two subunits, GB1 and GB2, to form a functional receptor. Whereas the molecular and functional characteristics of GABA(B) receptors have been recently extensively studied, the mechanisms underlying receptor de...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.09.002
更新日期：2003-11-14 00:00:00
abstract：:Several aspects of the role of corticotropin-releasing factor (CRF) in the forced swimming test were investigated in this study by using two different administration schedules. I.c.v. microinjection of CRF produced a dose-dependent increase in swimming activity when the administration schedule originally reported for ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01515-x
更新日期：1998-02-05 00:00:00
abstract：:We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mT...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94186-2
更新日期：1990-12-04 00:00:00
abstract：:The open field is a very popular animal model of anxiety-like behavior. An overview of the literature on the action elicited by effective or putative anxiolytics in animal subjected to this procedure indicates that classical treatments such as benzodiazepine receptor full agonists or 5-HT(1A) receptor full or partial ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(03)01272-x
更新日期：2003-02-28 00:00:00
abstract：:5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF), a fluorine-18-labeled analogue of the benzodiazepine antagonist flumazenil, was evaluated for use with positron emission tomography (PET). PET imaging of a baboon after i.v. injection of [18F]FEF showed that the radiofluorinated ligand rapidly localized in vivo within benz...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90153-u
更新日期：1992-07-21 00:00:00
abstract：:Since the discovery of first antidepressants in mid-1950's, the field has been intensively studied. Several new classes of compounds emerged and several hypotheses on the mechanism of their action were proposed. The novel antidepressants are either selective and reversible monoamine oxidase inhibitors, (e.g., moclobem...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(00)00565-3
更新日期：2000-09-29 00:00:00
abstract：:The ability of angiotensin II (A II) and 5-hydroxytryptamine (5-HT) to depolarise the rat isolated nodose ganglion preparation was examined. 5-HT depolarised the nodose ganglion, both at room temperature (20-24 degrees C) and at 35-37 degrees C. However, A II depolarised the nodose ganglion only under the latter condi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90217-t
更新日期：1990-08-21 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most smooth muscles. Although S1P has been shown to contract bladder smooth muscle, the mechanism(s) by which S1P initiates contraction has not been extensively investigated. The goal of this study was to determine if S1P-induced force generation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.10.004
更新日期：2013-11-15 00:00:00
abstract：:Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease pathogenesis leading to inflammation and destruction of synovial tissue in the joint. Several molecules lead to activation of immune pathways, including autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can cooperate to ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.03.085
更新日期：2016-05-05 00:00:00
abstract：:Inhibition of inducible nitric oxide (NO) synthase during endotoxaemia may be of therapeutic value. We have previously shown that pretreatment of mice with adenosine receptor agonists 1 h before lipopolysaccharide administration results in a dose-dependent reduction of plasma nitrite and nitrate (NOx-) levels. This re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00677-2
更新日期：1996-12-05 00:00:00
abstract：:Previous examinations demonstrated antidystonic effects of the synaptic vesicle protein 2A (SV2A) ligand levetiracetam in the dt(sz) mutant hamster, an animal model of paroxysmal non-kinesiogenic dyskinesia in which dystonic episodes can be induced by stress. In the present study, we examined the effects of the two ne...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.10.048
更新日期：2008-12-28 00:00:00
abstract：:The effect of cannabinoid receptor activation and blockade on the propulsive activity in the mouse small intestine was assessed in the present study by measuring the transit of an orally administered, non-absorbable marker. The cannabinoid receptor agonist WIN 55,212-2 (R(+)-[2,3-dihydro-5-methyl-3[(morpholinyl)methyl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01555-0
更新日期：1998-02-26 00:00:00
abstract：:Flavonoids are polyphenols frequently consumed in the diet they have been suggested to exert a number of beneficial actions on human health, including anti-inflammatory activity. This study investigated the immunomodulatory effects of two flavonoids, Chrysin and Hesperetin. The effects of flavonoids on B and T cell pr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.07.017
更新日期：2017-10-05 00:00:00
abstract：:Although a number of muscarinic agonists have been used in clinical trials for Alzheimer's Disease, many of these compounds are low in potency and have only limited intrinsic efficacy. The present study describes four non-quaternary oxadiazole based muscarinic agonists from a quinuclidine and a 1-azanorbornane series....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90006-r
更新日期：1990-10-09 00:00:00
abstract：:The cyclooxygenase (COX) pathway and prostanoids may critically contribute to the early allergic airway response. In the rat lung, serotonin (5-HT) is a major mediator of antigen-induced contractions. The aim of this study was therefore to examine the relative role of the COX pathway and serotonin for antigen-induced ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.11.039
更新日期：2013-01-15 00:00:00
abstract：:Rutin exhibits antidiabetic, antioxidant and anti-inflammatory properties, which makes rutin an attractive candidate for diabetic complications. The present study was designed to investigate the potential effect of rutin on diabetic neuropathy. After induction of diabetic neuropathy, rutin (5mg/kg, 25mg/kg and 50mg/kg...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.12.021
更新日期：2016-01-15 00:00:00
abstract：:We investigated the involvement of p160ROCK (a Rho-associated coiled coil-forming protein kinase), one of Rho kinases on superoxide anion production (O(2)(-) production), aggregation and adhesion of human polymorphonuclear leukocytes under physiological condition, using a selective p160ROCK inhibitor, (+)-(R)-trans-4-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00593-8
更新日期：2000-09-08 00:00:00
abstract：:Clinically, dexamethasone is known to reduce cerebral edema. To further investigate the mechanism of this neuroprotection, an in vitro model of brain-derived microvessel endothelial cells (BME cells) was used to investigate the effect of dexamethasone on hypoxia-induced hyperpermeability. Furthermore, the expression o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00915-8
更新日期：2001-01-12 00:00:00
abstract：:The effects of intracisternal injections of [Lys8]vasopressin and [Arg8]vasopressin (25, 50, 100, 200 mU/kg) and related compounds oxytocin (25, 50, 100, 200 mU/kg), felypressin (25, 50, 100, 200 mU/kg) and vasotocin (100, 200, 400, 800 ng/kg) on the acute neurogenic pressor responses to afferent vagal stimulation (5,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90009-3
更新日期：1985-11-19 00:00:00
abstract：:By far the most attention has been paid to the deleterious actions of nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract, particularly the gastric and duodenal mucosa. However, recent studies confirm a relatively high...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2004.07.042
更新日期：2004-10-01 00:00:00
abstract：:We investigated the role of interleukin-1 in the induction of a Ca(2+)-independent nitric oxide (NO) synthase by bacterial endotoxin in vivo. In anaesthetized rats, pretreatment with interleukin-1 receptor antagonist (interleukin-1ra; 16 mg kg-1 i.v., followed by an infusion of 2.4 mg kg-1 h-1) ameliorated the delayed...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90634-t
更新日期：1993-11-30 00:00:00
abstract：:We previously reported that intracerebroventricularly (i.c.v.) administered (±)-epibatidine (a potent agonist of nicotinic acetylcholine receptors) (1, 5 and 10 nmol/animal) dose-dependently elevated plasma levels of noradrenaline and adrenaline and that this response was reduced by i.c.v. administered indomethacin (c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.07.017
更新日期：2012-09-15 00:00:00
