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D2 Receptor Antagonist (d2 + receptor_antagonist)
Kinds of D2 Receptor Antagonist Selected AbstractsDiscovery of Orally Active Prostaglandin D2 Receptor Antagonists.CHEMINFORM, Issue 3 2005Kazuhiko Torisu Abstract For Abstract see ChemInform Abstract in Full Text. [source] GABAergic mechanism mediated via D1 receptors in the rat periaqueductal gray participates in the micturition reflex: an in vivo microdialysis studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Takeya Kitta Abstract The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and ,-aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation using in vivo microdialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D1 receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D1 receptor blockade. The D1 receptor antagonist prevented micturition-induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D2 receptor antagonist nor a D1/D2 receptor agonist affected these neurochemical and physiological parameters. Micturition-induced inhibition of GABA was not observed in 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of Parkinson's disease. 6-OHDA-lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D1 receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D1 receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6-OHDA-lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson's disease. [source] Opposite regulation by typical and atypical anti-psychotics of ERK1/2, CREB and Elk-1 phosphorylation in mouse dorsal striatumJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Laura Pozzi Abstract The two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), are involved in the control of gene expression via phosphorylation and activation of the transcription factors cyclic AMP response element binding protein (CREB) and Elk-1. Here, we have examined the effect of haloperidol and clozapine, two anti-psychotic drugs, and eticlopride, a selective dopamine D2 receptor antagonist, on the state of phosphorylation of ERK1/2, CREB and Elk-1, in the mouse dorsal striatum. Administration of the typical anti-psychotic haloperidol stimulated the phosphorylation of ERK1/2, CREB and Elk-1. Virtually identical results were obtained using eticlopride. In contrast, the atypical anti-psychotic clozapine reduced ERK1/2, CREB and Elk-1 phosphorylation. This opposite regulation was specifically exerted by haloperidol and clozapine on ERK, CREB, and Elk-1 phosphorylation, as both anti-psychotic drugs increased the phosphorylation of the dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) at the cyclic AMP-dependent protein kinase (PKA) site. The activation of CREB and Elk-1 induced by haloperidol appeared to be achieved via different signalling pathways, as inhibition of ERK1/2 activation abolished the stimulation of Elk-1 phosphorylation without affecting CREB phosphorylation. This study shows that haloperidol and clozapine induce distinct patterns of phosphorylation in the dorsal striatum. The results provide a novel biochemical paradigm elucidating the molecular mechanisms underlying the distinct therapeutic actions of typical and atypical anti-psychotic agents. [source] Central Bromocriptine-Induced Tachycardia is Reversed to Bradycardia in Conscious, Deoxycorticosterone Acetate-Salt Hypertensive RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2001Saad Lahlou The present study investigated the effect of bromocriptine on heart rate and the principal site of action of this agonist in conscious, deoxycorticosterone acetate-salt hypertensive rats, in which altered central dopaminergic activity has been previously reported. Intravenous administration of bromocriptine (150 ,g/kg) increased heart rate (49±5 beats/min.) in uninephrectomized control rats, while it induced a significant bradycardia (50±6 beats/min.) in deoxycorticosterone acetate-salt hypertensive rats. In the latter animals, intravenous (500 ,g/kg) or intrathecal (40 ,g/rat at T9,T10) pretreatment with domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier, reduced partially, but significantly, the bradycardiac responses to bromocriptine (reduction of about 44% and 48% of the maximal effect, respectively). In contrast, the bromocriptine-induced bradycardia was fully abolished by intravenous pretreatment with metoclopramide (300 ,g/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with intravenous and intrathecal domperidone. These results indicate that, in deoxycorticosterone acetate-salt hypertensive rats, bromocriptine decreases rather than increases heart rate, an effect that is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors. They further support the concept that, in normotensive, conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at both peripheral and spinal dopamine D2 receptors. [source] Potentiation of domperidone-induced catalepsy by a P-glycoprotein inhibitor, cyclosporin ABIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2003Kenji Tsujikawa Abstract The distribution of domperidone (DOM), a peripheral dopamine D2 receptor antagonist, to the brain is restricted by P-glycoprotein (P-gp) at the blood,brain barrier (BBB) and for this reason, DOM rarely causes parkinsonian symptoms, such as extrapyramidal side effects (EPS), unlike other dopamine D2 antagonists. In this study, we aimed to investigate whether cyclosporin A (CsA), a P-gp inhibitor, potentiates EPS induced by DOM. The intensity of EPS was assessed in terms of the duration of catalepsy in mice. D1, D2 and mACh receptor occupancies at the striatum were measured in vivo and in vitro. Moreover, the distribution of DOM to the brain was investigated by using an in situ brain perfusion technique. The intensity of DOM-induced catalepsy was significantly potentiated by the coadministration of CsA. The in vivo occupancies of D1, D2 and mACh receptors, as well as the brain distribution of DOM, were increased by CsA. These results suggest that CsA increases the brain distribution of DOM by inhibiting P-gp at the BBB, and potentiates catalepsy by increasing the occupancies of the D1 and D2 receptors. The risk of DOM-induced parkinsonism may be enhanced by the coadministration of CsA. Copyright © 2003 John Wiley & Sons, Ltd. [source] Antipsychotic combination therapy in schizophrenia.ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002A review of efficacy, risks of current combinations Objective:, To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials. Method:, A computerized Medline search supplemented by an examination of cross-references and reviews was performed. Results:, Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more ,tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment. Conclusion:, Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures. [source] Indirect modulation of dopamine D2 receptors as potential pharmacotherapy for schizophrenia: III.JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2002Retinoids Present antipsychotic drugs, whose clinical activity correlates with direct binding to dopamine D2 or other receptors, alleviate some of the symptoms of schizophrenia, but not all and not completely in many patients. In continuation of our overview of potential novel antipsychotic pharmacotherapy that would be based upon indirect modulation of dopamine or other neurotransmitter functioning, we focus in this article on the postulated use of retinoid analogs as novel antipsychotic agents. Several lines of evidence can be viewed as implicating retinoid dysregulation in schizophrenia, either as a causative or contributory factor. It has been proposed that using retinoid analogs to alter the downstream expression of dopamine D2 receptors might represent a novel approach to the treatment of the disease or amelioration of symptoms when used either as monotherapy or as adjunct pharmacotherapy to dopamine D2 receptor antagonists. [source] | |||||||||||||