Clonidine's estimates of platelet alpha2-adrenoreceptor (alpha2AR) density are substantially lower than yohimbine's. This discrepancy could have contributed to inconsistent results from studies on the role of alpha2AR in depression. Furthermore, few studies have investigated the relative distribution of alpha2AR between the high- and low-affinity states or their Gi protein coupling. [3H]yohimbine saturable binding to platelet alpha2AR, its displacement by norepinephrine and clonidine, and the effects of Gpp(NH)p on agonist displacement curves were investigated in 11 healthy volunteers. Clonidine estimates of alpha2AR density were close to norepinephrine estimates, and both were strongly correlated. Clonidine's K(L)/K(H) ratio was lower than norepinephrine's, consistent with its partial agonist nature. Norepinephrine and clonidine displacement curves revealed two affinity states. Gpp(NH)p induced a significant rightward shift to a single low-affinity state. When used in combination with a specific antagonist, clonidine's estimates of alpha2AR density were similar to those of norepinephrine's, and both were higher than previously reported, when clonidine was used alone. Re-evaluation of previous studies on alpha2AR in depression using clonidine is needed. The combined use of antagonist-saturation and agonist-displacement experiments to examine possible dysregulation in alpha2AR coupling to Gi protein in psychiatric disorders is recommended.
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http://dx.doi.org/10.1016/s0165-1781(99)00004-9 | DOI Listing |
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric psychiatric disorders and is frequently diagnosed and treated by pediatricians. Stimulant medications are the first-line treatment for ADHD but may not be a good fit for many patients due to side effects, inadequate treatment response, or family preference. Non-stimulant ADHD medications provide a useful alternative for patients that cannot tolerate stimulants, have an incomplete treatment response to stimulants, are at risk for stimulant diversion, or whose family prefers to avoid stimulants.
View Article and Find Full Text PDFJ Alzheimers Dis
September 2024
Department of Drug and Health Sciences, University of Catania, Catania, Italy.
Background: Sigma-1 receptors are highly expressed in brain areas related to cognitive function and are a promising target for anti-amnesic treatments. We previously showed that activation of sigma-1 receptors by the selective agonist compound methyl(1 R,2 S/1 S,2 R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropane carboxylate [(±)-PPCC] promotes a remarkable recovery in rat models of memory loss associated to cholinergic dysfunction.
Objective: In this study, we sought to assess the role of (±)-PPCC on working memory deficits caused by noradrenergic depletion.
INNOSC Theranostics Pharmacol Sci
July 2024
Department of Psychiatry, Mt. Sinai School of Medicine, New York City, New York, United States of America.
Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold .
View Article and Find Full Text PDFJ Addict Med
November 2024
From the College of Medicine, University of Nebraska Medical Center, Omaha, NE (NJM); and Department of Psychiatry, University of Nebraska Medical Center, Omaha, NE (VMMK, AAB).
Background: Malignant catatonia is a potentially lethal neuropsychiatric syndrome characterized by psychomotor abnormalities and autonomic instability. Patients with this syndrome require immediate treatment. Various psychiatric conditions and nonpsychiatric medical problems can trigger malignant catatonia.
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