Abstract:
:We previously reported the synthesis of three new opioid agonists as well as their in vitro and in vivo activity [Girón, R., Abalo, R., Goicoechea, C., Martín, M.I., Callado, L.F., Cano, C., Goya, P., Jagerovic, N. 2002. Synthesis and opioid activity of new fentanyl analogs. Life Sci. 71, 1023-1034]. One of them, N-[1-phenylpyrazol-3-yl]-N-[1-(2-phenethyl)-4-piperidyl)] propenamide (IQMF-4), showed an interesting antinociceptive activity. Intraperitoneally (i.p.) administered, it was as effective as fentanyl or morphine, being less potent than fentanyl but more so than morphine. The aim of the present work was to evaluate its antinociceptive effect by different routes of administration, using the hot plate test, and to investigate possible side effects, such as tolerance and withdrawal, in vitro, using the myenteric plexus-longitudinal muscle strip preparation from guinea pig ileum, and in vivo, using the hot plate test. IQMF-4 was more potent than morphine when administered per os (p.o.), but less potent when administered intracerebroventricularly (i.c.v.). By both routes, fentanyl is more potent that IQMF-4. When IQMF-4 was administered i.p., naloxone methiodide, a peripherally acting antagonist, was able to completely block its antinociceptive effect, whereas, after i.c.v. administration, the blockade was only partial. An interesting feature of the new compound is that it induces tolerance in vitro but not in vivo. Moreover, though in vitro withdrawal was not different from fentanyl or morphine, in vivo withdrawal symptoms were significantly less frequent in mice treated with IQMF-4 than in those treated with morphine or fentanyl. Although more assays are required, these results show that IQMF-4 appears to be a potent analgesic compound with an interesting peripheral component, and reduced ability to induce dependence.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Goicoechea C,Sánchez E,Cano C,Jagerovic N,Martín MIdoi
10.1016/j.ejphar.2008.07.052subject
Has Abstractpub_date
2008-10-24 00:00:00pages
22-9issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(08)00807-8journal_volume
595pub_type
杂志文章abstract::The in vivo cardiovascular effect and in vitro vasorelaxant effect of harman, one of harmala alkaloids isolated from Peganum harmala, were examined in this study. Harman (1-10 mg/kg, i.v.) dose-dependently produced transient hypotension and long-lasting bradycardia in pentobarbital-anesthetized rats, which were attenu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00928-0
更新日期:2000-03-03 00:00:00
abstract::Using the radioactive microsphere technique in anaesthetized pigs, we studied the systemic and carotid haemodynamic effects of intracarotid infusions (0.3, 1, 3 and 10 micrograms/kg.min) of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969), a drug with high affinity for 5-HT1A and 5-HT1B reco...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90432-9
更新日期:1989-11-14 00:00:00
abstract::The metabotropic glutamate receptor subtype 5 (mGlu5) and glutamatergic neurotransmission are associated with the pathophysiology of disorders such as anxiety, depression or chronic pain. Human and rat mGlu5 receptors have been cloned and characterized previously. We now describe the cloning of the mouse mGlu5b recept...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.10.004
更新日期:2008-01-28 00:00:00
abstract::This study examined whether the antinociceptive activity of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a GABA agonist, is mediated through an action exerted at the level of the spinal cord. Intrathecal injection of doses of THIP devoid of motor effects (1-2 micrograms) did not increase tail flick or hot pl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90197-3
更新日期:1984-08-03 00:00:00
abstract::Inflammation, closely associated with obesity, is emerging as an important risk factor for the pathophysiological development of atherosclerosis and diabetes mellitus. Fat balance is critical in the aetiology of obesity. Lipoprotein lipase is an important enzyme in lipid metabolism. The aim of this study was to invest...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.04.032
更新日期:2006-07-01 00:00:00
abstract::In this study we investigated if sodium nitroprusside (NaNP), a vasodilator with direct action on smooth muscle, would have any effect on calcium kinetics in blood vessels. The effect of NaNP, in 0.1-10 micrometer concentration, was studied in vitro on the uptake of 45Ca with the lanthanum method and on the efflux of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90052-8
更新日期:1977-09-01 00:00:00
abstract::Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and is the 4th leading cause of death worldwide. It is believed that an exaggerated inflammatory response to cigarette smoke causes progressive airflow limitation. This inflammation, where macrophages, neutrophils and T lymphocytes ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2015.03.029
更新日期:2015-07-15 00:00:00
abstract::NP-252, a new dihydropyridine derivative, and nifedipine non-competitively inhibited contractile responses to KCl and responses to Ca2+ in Ca(2+)-free medium containing KCl in rabbit aorta and renal, mesenteric, coronary and basilar arteries, mesenteric veins and vena cava. The effects of NP-252 in these smaller arter...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90888-w
更新日期:1991-10-22 00:00:00
abstract::Administration of endothelin to inactin-anesthetized rats resulted in a significant renal vasoconstriction as evidenced by a reduction in both renal plasma flow and glomerular filtration rate. Infusion of the novel nonpeptide endothelin ETA/ETB receptor antagonist, (+/-)-SB 209670, [(1RS-2SR,3RS)-3-(2-carboxymethoxy-4...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00591-9
更新日期:1995-12-29 00:00:00
abstract::Angiogenesis is critical for re-establishing blood supply to the ischemic myocardium after acute myocardial infarction (AMI). This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.172954
更新日期:2020-04-05 00:00:00
abstract::The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and eve...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.08.048
更新日期:2011-11-16 00:00:00
abstract::Microglia initially undergo rapid activation in response to injury and stressful stimuli, such as hypoxia. Oxidative stress and the inflammatory response play critical roles in hypoxic-ischemic brain injury. Carvedilol is a β-blocker used to treat high blood pressure and heart failure. In this study, we investigated w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.08.013
更新日期:2017-11-05 00:00:00
abstract::Paclitaxel, an antitumoral drug, was used in a single dose (29 mg/kg i.p.) as an injury agent for inducing transient suppression of hematopoiesis in a murine experimental model during 10days. The aim of this study focuses on erythropoietin (EPO) receptor, GATA binding protein 1 (globin transcription factor 1) (GATA-1)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.02.056
更新日期:2010-06-25 00:00:00
abstract::Previous work has demonstrated that neuropeptide tyrosine (NPY), Y(1) receptor and Y(2) receptor are critical in modulation of pain after nerve injury. We hypothesized that NPY was important for nociception after surgical incision. As a model of postoperative pain, rats underwent a plantar incision in one hindpaw. Wes...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.10.036
更新日期:2013-01-05 00:00:00
abstract::In cats anaesthetized with chloralose--urethane (70/100 mg/kg) a somato-sympathetic reflex increase of blood pressure and heart rate was evoked by electrical stimulation of sensory fibres running within the tibial nerve. I.V. injection of 30 microgram/kg of the alpha-adrenoceptor agonist clonidine caused a reflex inhi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90392-8
更新日期:1978-01-15 00:00:00
abstract::Canine femoral arteries responded to acetylcholine with relaxations; these were abolished in potassium free solution, restored by potassium or rubidium but not by cesium or amonium. Potassium and rubidium were equipotent in inducing ouabain-sensitive relaxation, while amonium and cesium were less potent. The results (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90027-8
更新日期:1980-10-03 00:00:00
abstract::Nicotine has been well established as an impulsive action-inducing agent, but it remains unknown whether endogenous acetylcholine affects impulsive action via nicotinic acetylcholine receptors. In the present study, the 3-choice serial reaction time task (3-CSRTT), a simple and valid assessment of impulsive action, wa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.05.028
更新日期:2010-09-01 00:00:00
abstract::Alzheimer's disease is the most frequent cause of dementia. Family and twin studies have suggested that genetic factors play a role in Alzheimer's disease development. Some Alzheimer's disease cases show an autosomal dominant inheritance pattern and thus allow the discovery of major disease genes. However, most Alzhei...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0014-2999(00)00903-1
更新日期:2001-01-19 00:00:00
abstract::Tracazolate (ICI 136,753) 4-butylamine-1-ethyl-6-methyl-1H-pyrazolo[3,4]pyridine-5-carboxylic acid ethyl ester is a non-benzodiazepine with anxiolytic-like activity in animal models. In contrast to the benzodiazepines, it enhances [3H]flunitrazepam binding in rat synaptic membrane fragments. The enhancement is potenti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90033-4
更新日期:1982-03-12 00:00:00
abstract::The effects of (-)-(R)-2-methyl-3-(1-pyrrolidinyl)-4'- trifluoromethylpropiophenone monohydrochloride (NK433), a novel centrally acting muscle relaxant, on masticatory muscle reflexes were investigated in rats. NK433 inhibited the monosynaptic tonic vibration reflex of the masseter muscle and the polysynaptic tonic pe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00783-0
更新日期:1996-02-29 00:00:00
abstract::Administration of drugs activating cannabinoid CB(1) receptors in the brain induces memory deficit in rodents, and blockade of these receptors may restore memory capacity in these animals. Central administration of beta-amyloid or beta-amyloid fragments may also lead to memory disturbances. This study was undertaken t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.08.026
更新日期:2003-09-23 00:00:00
abstract::The effect of dl-p-chloroamphetamine, fluoxetine and probenecid on the efflux of endogenous 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) into superfusates of the spinal cord of anesthetized rats was examined. Mean basal efflux of 5HT and 5HIAA was 0.27 and 15.56 ng/ml superfusate, respectively. The...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(83)90083-3
更新日期:1983-03-04 00:00:00
abstract::Anthracycline derivatives including 4'-epidoxorubicin are known to cause cardiovascular side effects. In this study we examined the effects of 4'-epidoxorubicin on sympathetic nerves of rat tail artery in vitro. Treatment with 4'-epidoxorubicin at concentrations higher than 10 microM gradually increased the resting te...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00505-6
更新日期:1998-08-28 00:00:00
abstract::The aim of the present study was to investigate the contribution of extracellular signal regulated kinase-1/2 (ERK1/2) to pulmonary artery contraction in response to 4-aminopyridione (4-AP), an inhibitor of a voltage-gated K(+) channels that regulate pulmonary vascular tone. Pulmonary artery rings 1-1.5 mm in diameter...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.04.042
更新日期:2007-08-13 00:00:00
abstract::Our previous research showed that ATP and adenosine 5'-O-2-thiodiphosphate (ADPbetaS) induce contractile effects in the longitudinal muscle of mouse distal colon via activation of P2Y receptors which are not P2Y(1) or P2Y(12) subtypes. This study investigated the nature of the P2Y receptor subtype(s) and the mechanism...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.07.057
更新日期:2008-10-24 00:00:00
abstract::The antagonist effects of ketanserin and 2'-methyl-4'-(5-methyl-1,2,4)oxadiazol-3-yl)-biphenyl-[4-carboxyli c acid 4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127,935) were compared to naratriptan-induced inhibition of cAMP formation in C6-glial cell lines stably expressing human 5-HT1D or 5-HT1B receptor ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00011-8
更新日期:1996-04-04 00:00:00
abstract::The mechanisms of ryanodine-induced contractions were studied in strips of femoral arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ryanodine (30 nM to 30 microM) alone contracted arterial strips in a dose-dependent manner. The maximum contraction in SHR was about 5 times g...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90383-2
更新日期:1994-03-11 00:00:00
abstract::Recent data show that corticolimbic expression of the effector immediate early gene Arc is up-regulated by standard antidepressant drugs. Here, we tested the effect upon Arc expression of a novel antidepressant and selective 5-hydroxytryptamine/noradrenaline reuptake inhibitor (SNRI), (-)1-(1-dimethylaminomethyl) 5-me...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2004.03.002
更新日期:2004-04-12 00:00:00
abstract::The effect of potassium on the binding of digoxin or digoxigenin to isolated Na+, K+-ATPase was compared with that of potassium on the positive inotropic action of the agents in guinea-pig hearts. The binding of digoxigenin to the enzyme in vitro was reduced to a greater extent by potassium than was the binding of dig...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90497-7
更新日期:1979-08-15 00:00:00
abstract::The influence of endothelin-1 on nociception induced by capsaicin was assessed in the mouse hindpaw. Local endothelin-1 injection (1 to 20 pmol/paw) 30 min prior to ipsilateral injection of capsaicin (0.1 microg/paw) increased, in a graded fashion, the time spent licking the injected paw. Maximal hyperalgesia was obta...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00281-7
更新日期:1998-06-12 00:00:00