scholarly journals Analogues of (3R)-7-Hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic). Synthesis and in Vitro and in Vivo Opioid Receptor Antagonist Activity

2010 ◽  
Vol 53 (14) ◽  
pp. 5290-5301 ◽  
Author(s):  
Scott P. Runyon ◽  
Lawrence E. Brieaddy ◽  
S. Wayne Mascarella ◽  
James B. Thomas ◽  
Hernán A. Navarro ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Antagonist Activity ◽  
Opioid Receptor Antagonist

Novel endomorphin-2 analogs with mu-opioid receptor antagonist activity

2005 ◽  
Vol 66 (3) ◽  
pp. 125-131 ◽  
Author(s):  
R. Kruszynski ◽  
J. Fichna ◽  
J.-C. do-Rego ◽  
N.N. Chung ◽  
P.W. Schiller ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Antagonist Activity ◽  
Mu Opioid ◽  
Opioid Receptor Antagonist

Central opioid receptors mediate glucoprivic inhibition of pituitary LH secretion

1997 ◽  
Vol 272 (4) ◽  
pp. E517-E522 ◽  
Author(s):  
K. P. Briski
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Hormone Secretion ◽  
Male Rats ◽  
Pituitary Hormone ◽  
Intracerebroventricular Administration ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Antagonists

The present studies investigated the significance of glucoprivic metabolic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular administration of 2-DG was also efficacious in suppressing circulating LH; animals treated with either of the two highest doses of the drug exhibited a significant reduction in plasma LH. In vitro studies examined direct effects of 2-DG on pituitary gonadotrope secretory activity. Exposure of anterior pituitary tissue to 2-DG during short-term perfusion had no significant impact upon either basal or gonadotropin-releasing hormone-stimulated LH release. Finally, groups of GDX rats were pretreated by intracerebroventricular administration of either the nonselective opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor antagonists were observed to attenuate the suppressive effects of 2-DG on circulating LH in these animals. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.

scholarly journals Novel18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of18F-LY2459989 in Nonhuman Primates

2017 ◽  
Vol 59 (1) ◽  
pp. 140-146 ◽  
Author(s):  
Songye Li ◽  
Zhengxin Cai ◽  
Ming-Qiang Zheng ◽  
Daniel Holden ◽  
Mika Naganawa ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Nonhuman Primates ◽  
In Vivo Evaluation ◽  
Opioid Receptor Antagonist

Endogenous Activation of Supraoptic Nucleus κ-Opioid Receptors Terminates Spontaneous Phasic Bursts in Rat Magnocellular Neurosecretory Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 3235-3244 ◽  
Author(s):  
Colin H. Brown ◽  
Gareth Leng ◽  
Mike Ludwig ◽  
Charles W. Bourque
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Random Element ◽  
Plateau Potentials ◽  
Phasic Activity ◽  
Potential Amplitude ◽  
Opioid Receptor Antagonist ◽  
Plateau Potential ◽  
Dynorphin Release

Phasic activity in magnocellular neurosecretory vasopressin cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials (spikes) are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials (DAPs). Burst termination is believed to result from autocrine feedback inhibition of plateau potentials by the κ-opioid peptide, dynorphin, which is copackaged in vasopressin neurosecretory vesicles and exocytosed from vasopressin cell dendrites during phasic bursts. Here we tested this hypothesis, using intracellular recording in vitro to show that κ-opioid receptor antagonist administration enhanced plateau potential amplitude to increase postspike excitability during spontaneous phasic activity. The antagonist also increased postburst DAP amplitude in vitro, indicating that endogenous dynorphin probably reduces plateau potential amplitude by inhibiting the DAP mechanism. However, the κ-opioid receptor antagonist did not affect the slow depolarization that follows burst termination, suggesting that recovery from endogenous κ-opioid inhibition does not contribute to the slow depolarization. We also show, by extracellular single-unit recording, that that there is a strong random element in the timing of burst initiation and termination in vivo. Administration of a κ-opioid receptor antagonist eliminated the random element of burst termination but did not alter the timing of burst initiation. We conclude that dendritic dynorphin release terminates phasic bursts by reducing the amplitude of plateau potentials to reduce the probability of spike firing as bursts progress. By contrast, dendritic dynorphin release does not greatly influence the membrane potential between bursts and evidently does not influence the timing of burst initiation.

The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist

2013 ◽  
Vol 386 (6) ◽  
pp. 479-491 ◽  
Author(s):  
Pamela R. Tsuruda ◽  
Ross G. Vickery ◽  
Daniel D. Long ◽  
Scott R. Armstrong ◽  
David T. Beattie
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Pharmacological Profile ◽  
Opioid Receptor Antagonist
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