Abstract:
:Aripiprazole is the first dopamine D(2)/D(3) receptor partial agonist approved for use in the treatment of psychiatric disorders including schizophrenia, bipolar disorder, and unipolar depression in the US. Aripiprazole has demonstrated a relatively favorable side effect profile compared to other commonly prescribed antipsychotics, including a low propensity for treatment-limiting extrapyramidal symptoms, hyperprolactinemia, and body weight gain. In an effort to elucidate aripiprazole's pharmacological activity in relation to clinically relevant fluctuation of dopamine D(2) receptor reserves, we compared the properties of aripiprazole to other antipsychotics, quetiapine, clozapine, olanzapine, ziprasidone, risperidone and haloperidol, a dopamine D(2) receptor partial agonist, bifeprunox, dopamine D(3) receptor modulators, BP897 (N-[4-[4-(2-Methoxyphenyl)-1-piperazinyl]butyl]naphthalene-2-carboxamide) and GR103691 (4'-Acetyl-N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]biphenyl-4-carboxamide), and a 5-HT(1A) partial agonist, buspirone using forskolin-stimulated cAMP accumulation in clonal Chinese hamster ovary cell lines expressing low and high densities of human dopamine D(2S) receptors (hD(2S)-Low and hD(2S)-High, respectively). In hD(2S)-Low cells lacking receptor reserves for dopamine, all drugs antagonized dopamine responses, and their potencies correlated well with respective affinities. In hD(2S)-High cells possessing receptor reserves, all antipsychotics except aripiprazole antagonized dopamine responses, and their antagonist potencies were less than those in hD(2S)-Low cells treated with the equal dopamine concentration. In contrast, aripiprazole and bifeprunox acted as full agonists. BP897, GR103691 and buspirone acted as partial agonists. These data suggest that the level of receptor reserves influences antagonist potencies and side effects associated with antipsychotics. Aripiprazole's unique receptor reserve dependent properties may account for its favorable tolerability in the clinical setting.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Tadori Y,Forbes RA,McQuade RD,Kikuchi Tdoi
10.1016/j.ejphar.2009.02.007subject
Has Abstractpub_date
2009-04-01 00:00:00pages
35-40issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(09)00146-0journal_volume
607pub_type
杂志文章abstract::Recent successes as a pharmacological adjunct to exposure therapy has focused attention on the therapeutic potential of the glycine(B) receptor partial agonist, D-cycloserine (DCS), in certain clinical anxiety disorders. Although widely believed to reflect a facilitation of extinction learning, previous research with ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.08.005
更新日期:2010-11-10 00:00:00
abstract::Colorectal cancer (CRC) has become one of the major factors of tumor-related morbidity and mortality in the world because of its poor prognosis and consequences of metastatic spread. Currently, chemoprevention has been considered as a way of preventing cancer who takes advantage of plant phytochemicals and synthetic c...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2020.173588
更新日期:2020-11-15 00:00:00
abstract::In the presence of 3 x 10(-6) M captopril, 5 x 10(-7) M des-Asp-Angiotensin I was found to inhibit the electrically (1 and 2 Hz) induced contraction of the rabbit pulmonary artery but had no significant effect on the noradrenaline-stimulated contraction. 2.8 x 10(-6) M indomethacin and 10(-6) M losartan but not 10(-6)...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00461-s
更新日期:1995-09-15 00:00:00
abstract::The nerve growth factor (NGF) is a neurotrophic factor essential for the development and survival of neurons. It has also been identified as a mediator of inflammation and can cause airway hyperresponsiveness [Frossard et al., Eur. J. Pharmacol. 500, 453 (2004)]. Evidence in rodents suggests a link between tachykinins...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.10.068
更新日期:2007-04-10 00:00:00
abstract::The present study concerns previously unreported effects of menthol, a cyclic terpene alcohol produced by the peppermint herb, on anion transporters in polarized human airway Calu-3 epithelia. Application of menthol (0.01-1mM) attenuated transepithelial anion transport, estimated as short-circuit currents (I(SC)), aft...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.03.032
更新日期:2010-06-10 00:00:00
abstract::In the present study, we reported the metabolic effects of salidroside, one of the active components of Rhodiola Rosea, on skeletal muscle cells. Salidroside dose-dependently stimulated glucose uptake in differentiated L6 rat myoblast cells. Inhibitor of AMP-activated protein kinase (AMPK) by pretreating the cells wit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.04.036
更新日期:2008-07-07 00:00:00
abstract::In previous studies, we have shown that opioid agonists ([D-Ala2, D-Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reactio...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00339-1
更新日期:1996-08-29 00:00:00
abstract::Bupropion is a weakly potent central nervous system (CNS) stimulant that is marketed both as an antidepressant and as an anti-smoking aid. The mechanism(s) by which it produces its effects is not well understood. In the present study, the effect of bupropion was examined in rats trained to discriminate the stimulus ef...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01554-6
更新日期:2002-05-17 00:00:00
abstract::Isolated rat mast cells were used to study whether ionophore A23187 could induce histamine release by mobilizing cellular calcium. The histamine release was a slow process which was completed after about 20 min incubation with A23187. The A23187-induced histamine release was inhibited after incubation of the cells wit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90100-4
更新日期:1980-04-04 00:00:00
abstract::Inhibition of intrathecal substance P-elicited behavior by mu-, delta- and kappa-opioids was compared. In both the substance P behavioral test and the tail flick antinociceptive test, intrathecal [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin (DADL) were equipotent, morphine and ethylketazocine were less...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90403-4
更新日期:1982-12-17 00:00:00
abstract::It has been reported that the antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) may result from the modulation of brain monoaminergic systems. However, the mechanisms of FDPI action are not fully understood. The aim of this study was to investigate the contribution of N-methyl-d-aspartate ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.04.046
更新日期:2016-07-05 00:00:00
abstract::Concanavalin A-induced hepatitis is often used as a model of liver injury. In this model, plasma tumor necrosis factor-alpha (TNF-alpha) level increased in concanavalin A-injected mice. Prophylactic treatment with Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl, significantl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.08.060
更新日期:2005-10-31 00:00:00
abstract::The inhibitory effects of a hypotensive agent, cadralazine and its metabolite, ISF-2405, on the level of cytosolic Ca2+ ([Ca2+]cyt) and on contractions were examined in isolated vascular smooth muscle. Cadralazine slightly inhibited the transient norepinephrine-induced contraction in rabbit aorta and canine femoral, r...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90472-i
更新日期:1990-03-20 00:00:00
abstract::Endothelin produced a concentration-dependent (1 nM-0.3 microM) contraction of isolated guinea-pig airways (trachea and main bronchi). The response was unaffected by tetrodotoxin (1 microM) and slightly depressed by indomethacin (5 microM) but promptly abolished by isoprenaline (1 microM) or EDTA (3 mM). In the bronch...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90670-5
更新日期:1989-01-24 00:00:00
abstract::Glucagon-like peptide-2 (GLP-2) is a potent, intestinal-specific trophic hormone. However, the relationship between the dose and timing of GLP-2 administration and these trophic effects is not clear. We investigated the effects of variations in the dose and timing of GLP-2 administration on its intestinal trophic acti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.07.070
更新日期:2008-10-31 00:00:00
abstract::The general anaesthetic ketamine affects the central cholinergic system in several manners, but its effect on spinal acetylcholine release, which may be an important transmitter in spinal antinociception, is unknown. This study aimed to investigate the effect of ketamine on spinal acetylcholine release. Microdialysis ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.01.044
更新日期:2006-03-18 00:00:00
abstract::We tested if discontinuation of cocaine self-administration can lead to the development of depressive-like symptoms in the forced swim test expressed as changes in immobility, swimming and climbing behaviors in rats. A "yoked" procedure in which rats were run simultaneously in groups of three, with two rats received t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2009.10.049
更新日期:2010-02-10 00:00:00
abstract::Substance P causes histamine release from rat peritoneal mast cells probably through direct activation of a specific G protein at micromolar concentrations. We found that peritoneal mast cells of a substrain of Wistar rats (Std:Wistar) responds to nanomolar concentrations of substance P by releasing histamine in a con...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00338-6
更新日期:1999-06-18 00:00:00
abstract::We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00337-x
更新日期:2000-06-23 00:00:00
abstract::Multiple high-dose administrations of the dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular dopamine uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the p...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01911-3
更新日期:2003-07-11 00:00:00
abstract::The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The rel...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.07.004
更新日期:2010-10-10 00:00:00
abstract::We used two experimental models to prove that resveratrol (trans-3,4',5-trihydroxystilbene) reduces cardiac ischemic-reperfusion injury by means of a nitric oxide- and adenosine-dependent mechanism. (1). ACUTE EX VIVO: resveratrol (10 microM, 10 min) infusion in Langendorff-perfused normoxic rat hearts significantly i...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01441-9
更新日期:2003-03-28 00:00:00
abstract::Piper longum L. has been used as a crude drug for the treatment of the disorder of peripherally poor blood circulation in Asia. In the present study, we examined the effect of piperlongumine, a constituent of P. longum L., on rabbit platelet aggregation. Piperlongumine concentration-dependently inhibited platelet aggr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.05.073
更新日期:2007-09-10 00:00:00
abstract::The effect of vasoactive intestinal polypeptide (VIP) on in vitro ACTH release and adenylate cyclase activity was investigated in human ACTH-secreting pituitary adenomas from 4 patients with Cushing's disease and 2 patients with Nelson's syndrome. In all the tumors tested, VIP elicited a dose-dependent stimulation of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90291-6
更新日期:1982-09-10 00:00:00
abstract::The paraventricular nucleus of the hypothalamus (PVN) contains dense orexin 2 (OX2) receptor. We examined the mechanisms of OX2 receptor-mediated excitation on electrophysiologically identified type I (putative magnocellular), low-threshold spikes (LTS)-expressing type II (putative preautonomic), and non-LTS type II (...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172802
更新日期:2020-02-15 00:00:00
abstract::Computer analysis of [125I]iodocyanopindolol competition studies using the relatively selective beta 1-adrenoceptor antagonist, ICI 89406, and the beta 2-selective antagonist, ICI 118551, on rabbit mononuclear leukocyte plasmalemmal preparations favored a two-site model indicating that both beta 1- and beta 2-adrenoce...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90502-5
更新日期:1989-01-31 00:00:00
abstract::Considerable evidence has appeared recently connecting the mechanism of action of some antidepressant drugs with the inhibition of the enzymes responsible for enkephalin degradation. Imipramine in vitro inhibits the enkephalin-degrading aminopeptidase MII and interacts with the enzyme in a mixed competitive-noncompeti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00686-4
更新日期:1998-10-30 00:00:00
abstract::Antagonists, but not agonists, of the 5-HT3 receptor are useful therapeutic agents, and it is possible that partial agonists may also be potentially useful in the clinic. Here we show that 5-fluorotryptamine (5-FT) is a partial agonist at both 5-HT3A and 5-HT3AB receptors with an Rmax (Imax/Imax 5-HT) of 0.64 and 0.45...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2007.11.014
更新日期:2008-02-12 00:00:00
abstract::The response of lymph vessels, arterioles and venules in the exteriorized rat mesentery to endothelin-1, vasopressin and norepinephrine was examined with the aid of high-resolution television microscopy. On a molar basis, endothelin-1 was more potent than vasopressin to contract the three types of vessels. Norepinephr...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(89)90135-0
更新日期:1989-10-24 00:00:00
abstract::The concentrations of p-tyramine (p-TA), m-tyramine (m-TA), dopamine (DA) and their principal metabolites, p-hydroxyphenylacetic acid (p-HPAA), m-hydroxyphenylacetic acid (m-HPAA) and homovanillic acid (HVA) were determined in the corpus striatum of Swiss mice at various times after the subcutaneous administration of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90261-8
更新日期:1982-09-24 00:00:00