Abstract:
:Pain is a global health challenge. For decades, we have been primarily relying upon opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management. However, adverse effects related to opioid and NSAID use are severe and often lead to forced drug discontinuation and inadequate pain relief. Despite decades of research, currently available pharmacotherapies for pain still fall short of clinical needs. Fortunately, with our increased understanding of the neurobiology and pathophysiology of pain, new drug targets have been emerging, which may lead to novel therapeutic strategies. This perspective will briefly review the theoretical development and experimental evidence of four emerging drug targets for pain treatment: transient receptor potential ankyrin (TRPA) 1 channel, cannabinoid CB(2) receptors, GABA(A) subtype receptors, and imidazoline I(2) receptors. Sustained efforts on these novel drug targets will increase the appreciation for these targets and expedite the development of lead compounds to reach clinical stage, which will undoubtedly strengthen our pharmacotherapeutic armaments against various debilitating painful conditions.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Li JX,Zhang Ydoi
10.1016/j.ejphar.2012.01.017subject
Has Abstractpub_date
2012-04-15 00:00:00pages
1-5issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(12)00068-4journal_volume
681pub_type
杂志文章,评审abstract::Stimulation of muscarinic M1-receptors in isolated rabbit vas deferens by McN-A-343 inhibited electrically induced twitch contractions susceptible to competitive blockade by (+)-, (+/-), (-)-telenzepine and pirenzepine (pA2 = 9.12, 8.86, 6.98 and 7.79, respectively). The inhibition of twitch contractions by 10(-6) M M...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90604-5
更新日期:1990-05-03 00:00:00
abstract::Lithium, commonly used to treat bipolar disorder, potentiates the ability of the muscarinic agonist pilocarpine to induce seizures in rodents. As this potentiation by lithium is reversed by the administration of myo-inositol, the potentiation may be mediated by inhibition of inositol monophosphatase (IMPase), a known ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173377
更新日期:2020-09-15 00:00:00
abstract::The coronavirus disease-19 (COVID-19) outbreak that is caused by a highly contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a zoonotic pandemic, with approximately 24.5 million positive cases and 8.3 lakhs deaths globally. The lack of effective drugs or vaccine provoked the research fo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173688
更新日期:2021-01-05 00:00:00
abstract::The non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), induces in rats a characteristic behavioural syndrome with ataxia, stereotypies and hyperlocomotion. At least part of this behavioural syndrome is thought to be related to interactions between glutamatergic and dopaminergic neurotransmission. Based on...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90029-4
更新日期:1992-05-14 00:00:00
abstract::Nerve growth factor (NGF) is known to regulate the development and survival of select populations of neurons via its binding/activation of the TrkA and p75(NTR) receptors. However, in some physiological circumstances NGF dysregulation can result in debilitating pathologies, including diabetic neuropathies, interstitia...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2013.03.029
更新日期:2013-05-15 00:00:00
abstract::N-methyl-d-aspartate (NMDA) receptors are important in mediating excitatory neurotransmission in the nervous system. They are preferentially inhibited by some general anesthetics and have, therefore, been implied in the mediation of their effects. This review summarizes the main research findings available related to ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2013.11.039
更新日期:2014-01-15 00:00:00
abstract::The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90609-l
更新日期:1993-05-19 00:00:00
abstract::Nitric oxide synthases (NOS) and cyclooxygenase-2 (COX-2) are important enzymes involved in ulcer healing but interactions between them have not been clearly defined. The aim of this study was to investigate the effects of selective or non-selective inhibition of NOS on the expression and activity of COX-2 during heal...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.12.088
更新日期:2006-05-01 00:00:00
abstract::Omega-3 polyunsaturated fatty acids have been reported to be associated with favorable changes in the respiratory system. To determine one of the mechanisms for this effect, membrane currents were recorded in guinea-pig tracheal myocytes by using the whole-cell voltage clamp technique. Without EGTA in the patch pipett...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00484-1
更新日期:1998-08-21 00:00:00
abstract::Acute (-)-nicotine administration (0.4 and 0.8 mg/kg s.c.) produced a regionally specific increase in the rate of catecholamine synthesis in the rat nucleus accumbens, hypothalamus and hippocampus but not elsewhere, including the caudate-putamen. In all regions rates of 5-hydroxytryptamine synthesis were unaffected. (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90440-8
更新日期:1989-08-29 00:00:00
abstract::We have previously demonstrated that treatment with L-cis diltiazem reduced cardiac infarct size in vivo. To examine the effect of L-cis diltiazem on Ca(2+) overload induced by ischemia/reperfusion, we used a model for Ca(2+) overload produced by metabolic inhibition in isolated guinea pig myocytes. Intracellular Ca(2...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00709-8
更新日期:1999-12-03 00:00:00
abstract::An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90811-7
更新日期:1994-12-27 00:00:00
abstract::Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquis...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.02.017
更新日期:2014-05-05 00:00:00
abstract::Nitric oxide (NO) has been described to exert various anti-atherogenic actions. However, NO, in some cases, has been shown to stimulate the oxidation of low-density lipoprotein (LDL), which constitute an important triggering event in atherosclerosis. Thus, some NO donors, despite their advantages, might also induce ox...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01166-9
更新日期:2001-08-03 00:00:00
abstract::Injection into the superior colliculus of anaesthetised rats of the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 micromol), but not its inactive enantiomer N(omega)-nitro-D-arginine methyl ester (D-NAME; 1 micromol), significantly (P < 0.01) increased the mean arterial blood p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)83029-4
更新日期:1997-06-05 00:00:00
abstract::Histamine-induced [3H]inositol monophosphate ([3H]IP1) accumulation in slices of rat cerebral cortex and guinea-pig cerebral cortex and cerebellum was inhibited in a concentration-dependent manner by Ni2+ ions. The effect of Ni2+ on the concentration-response curve for histamine in rat cerebral cortex was consistent w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(93)90100-n
更新日期:1993-05-15 00:00:00
abstract::Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in d...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2017.12.024
更新日期:2018-02-05 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::We have developed a model of ischaemia-reperfusion injury in C57BL/6 mice involving ischaemia for 0.5 to 2.5 h with an elastic tourniquet on one hind limb and reperfusion for 24 h, analogous to a well-established model of ischaemia-reperfusion injury in the rat. Viability was assessed in tissue homogenates of the gast...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01101-1
更新日期:1997-08-13 00:00:00
abstract::Gender-related differences in susceptibility to stress and stress-related disorders such as depression, and in response to treatment with antidepressants have been observed, but the underlying molecular mechanisms are still unknown. Considering the role of glucocorticoid hormones in the systemic reaction against stres...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.02.038
更新日期:2009-04-17 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::The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90502-w
更新日期:1990-06-21 00:00:00
abstract::In cultured rat heart muscle cells, reversible long-term ATP depletion induces a decrease in beta-adrenoceptor density and a fall in isoproterenol- as well as forskolin-stimulated cAMP formation. However, isoproterenol-stimulated adenylyl cyclase activity in membrane preparations is not reduced after ATP depletion. Th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(91)90104-p
更新日期:1991-11-13 00:00:00
abstract::Neurotrophic and neuroprotective properties of Hsp70 were studied in olfactory cortex slices of hypertensive rats under normal conditions and under influence of autologous blood (blood clot). Under normal conditions, synaptic response in slices depended on Hsp70 amount in medium. Incubation of slices with Hsp70 showed...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.12.004
更新日期:2012-02-29 00:00:00
abstract::1-Phenyl-3-(2-thiazolyl)-2-thiourea (200 mg/kg, 1 h) protected the adrenergic nerve plexus in the mouse atrium against the destructive action of i.v. 5,7-dihydroxytryptamine. Protection was also observed with ethanol (4 g/kg, 1 h) and with nialamide (50 mg/kg, 2 h). ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(77)90026-7
更新日期:1977-06-01 00:00:00
abstract::Two reserpine dosage schedules were applied to Wistar rats (a) 5 mg/kg i.p. 6 hr before sacrifice and (b) 5 mg/kg i.p. at 36, 24 and 12 hr prior to sacrifice. Control animals were correspondingly sham-injected. The coeliac-mesenteric ganglion complex was removed and processed either for the Falck-Hillarp fluorescence ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90258-7
更新日期:1975-12-01 00:00:00
abstract::Cisplatin is widely used chemotherapeutic drug and have some serious side effects as tissue toxicity and nausea and vomiting. Aprepitant is used in clinic as an anti-emetic drug for cisplatin treated patient to prevent nausea and vomiting. We aimed to investigate the protective effects of Aprepitant on cisplatin-induc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173168
更新日期:2020-08-05 00:00:00
abstract::The present study was undertaken to evaluate the effects of an adenylate cyclase activator N,N-dimethyl-beta-alanine[3R-(3alpha, 4alphabeta, 5beta, 6beta, 6aalpha, 10alpha, 10abeta, 10balpha)]-5(acetyloxy)-3-ethenyldodecahydro-10, 10b-dihydroxy-3, 4a, 7, 7, 10a-pentamethyl-1-oxo-1H-naphtho [2,1-b] pyran-6-yl ester hyd...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00220-4
更新日期:1999-05-21 00:00:00
abstract::The alpha 1-receptor agonist methoxamine reduced, by a prazosin sensitive mechanism, the nerve stimulation evoked release of norepinephrine in the rat caudal artery. The effect of methoxamine was also antagonized by the purinoceptor antagonist 8-(p-sulfophenyl)theophylline suggesting an involvement of endogenous purin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(91)90236-j
更新日期:1991-01-17 00:00:00
abstract::Nicotine produced antinociception in mice which was antagonized noncompetitively by naloxone. In addition, at significantly lower doses, nicotine noncompetitively antagonized morphine-induced antinociception. A speculative suggestion regarding the opiatergic and anti-opiatergic actions of nicotine is that it significa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(93)90009-f
更新日期:1993-12-01 00:00:00