Overview of Neurotransmission: Relationship to the Action of Antiepileptic Drugs
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
The alpha-1 adrenergic receptor mediates its action through another second messenger system, which is also linked to the receptor by a Gs protein. The second messengers produced when an agonist binds to the alpha-1 receptor are actually metabolites of phosphoinositide breakdown mediated by phospholipase C and include inositoltriphosphate (IP3) and diacyl-glycerol (DAG). IP3 causes the release of Ca2+ from intracellular storage sites and the Ca2+ can then activate protein kinases to produce phosphorylation of membrane proteins (Figure 4). The DAG activates protein kinase C which in turn can phosphorylate various proteins to mediate various cellular responses of alpha-1 agonists.3,11 The molecular structure of the alpha-1 receptor has not yet been determined, but the molecular weight determined by photoaffinity labeling procedures was found to be about 80,000.12
Vasopressors, Vasodilators, and Antithromboticsin The Catheterization Laboratory
Debabrata Mukherjee, Eric R. Bates, Marco Roffi, Richard A. Lange, David J. Moliterno, Nadia M. Whitehead in Cardiovascular Catheterization and Intervention, 2017
Norepinephrine and epinephrine exhibit mixed receptoractivity. Norepinephrine has potent beta-1 and alpha-adrenergic receptor activity, with less beta-2 activity. Thistranslates clinically into more potent vasoconstrictive prop-erties and less inotropic effects as compared with dopa-mine. For this reason, norepinephrine remains the initialcatecholamine of choice for septic or vasodilatory shock.Epinephrine is the most potent agonist for the beta-1, beta-2,and alpha-adrenergic receptors. Adverse effects—includingarrhythmias, ischemia, tachycardia, hyperglycemia, cerebralhemorrhage, pulmonary edema, and diminished splanchnicblood flow—limit use of continuous epinephrine infusion.As such, epinephrine should be reserved for patients who areunresponsive to dopamine or norepinephrine.21
Pharmacology of Catecholamines
Sam Kacew in Drug Toxicity and Metabolism in Pediatrics, 1990
Norepinephrine is the neurotransmitter of the sympathetic nervous system and is the biosynthetic precursor of epinephrine, differing only by a methyl group on its amino terminus (Figure 1). It possess both α- and β-adrenergic receptor activity. Low infusion doses produce mainly β-adrenergic effects, including increased cardiac contractility, conduction velocity, and chronotropy with little change in peripheral vascular resistance. More commonly, in the doses used during hypotensive shock, mixed α- and β-adrenergic effects occur. Peripheral vascular resistance is increased by α1-adrenergic-mediated vasoconstriction. Cardiac contractility, cardiac work, and stroke volume all increase if the augmentation in afterload is tolerated by the ventricle. Chronotropy is generally blunted by baroreceptor-mediated vagal effects which slow the heart rate in response to norepinephrine-induced increase in blood pressure.
Sublingual dexmedetomidine: repurposing an anesthetic as an anti-agitation agent
Published in Expert Review of Neurotherapeutics, 2023
Justin Faden, Meghan Musselman, Leslie Citrome
The alpha-2-adrenergic receptor is an autoreceptor that regulates the release of norepinephrine. Excess norepinephrine is a contributor to hyperarousal states such as agitation and panic. There are three subtypes of the alpha-2 adrenergic receptor, alpha-2A, alpha-2B, and alpha-2C, with alpha-2A being predominant in the locus coeruleus, a region of the brain associated with the arousal system [43,44]. Several alpha-2 adrenergic receptor agonists are currently available including clonidine, dexmedetomidine, guanfacine, and lofexidine. Of these options, dexmedetomidine has the highest affinity and highest intrinsic action on the alpha-2A receptor, thereby perhaps better positioned to ameliorate hyperarousal states[27]. Additionally, although dexmedetomidine is more sedating than clonidine due to greater selectivity for alpha 2 receptors than alpha 1 receptors (A2:A1 ratio 1620:1 vs 220:1), an important attribute of dexmedetomidine-based sedation is that patients remain easily arousable [45,46].
Impact of dissociative experiences in migraine and its close relationship with osmophobia
Published in Neurological Research, 2020
Hikmet Saçmacı, Gül Ferda Cengiz, Tülin Aktürk
Both functional tests and clinical findings show that sympathetic stimuli are diminished in migraine patients during attacks and interictal periods. It is known that alpha-adrenergic receptor sensitivity increases with a reduction in norepinephrine level [18]. As a result, findings that might be psychologically traumatic occur along with reduced sympathetic activity, such as pupillary enlargement, nausea-vomiting, orthostatic hypotension, revealing the main domains of migraine. The predominance of parasympathetic activity in migraineurs is consistent with autonomic dysfunction in the pathophysiology of dissociative symptoms [21]. Thirty percent of patients with dissociative experience exhibit psychophysiological hypersensitivity under extreme stress conditions, manifest blunted autonomic reactivity and sympathetic deinnervation occur [9,25]. This pathophysiological process shows that central noradrenergic system dysfunction is the basis of the symptoms [9].
Exploring detailed characteristics of autonomic dysreflexia
Published in The Journal of Spinal Cord Medicine, 2018
Ryan Solinsky, Steven C. Kirshblum, Stephen P. Burns
Chronicity of SCI demonstrated a strong positive linear correlation with increased pharmacologic time to resolution of AD episodes. This is consistent with emerging evidence for ongoing evolution within the spinal cord well after the initial injury, where both a greater degree of AD6 and a higher rate of detrusor sphincter dyssynergia18 have been noted as SCI becomes more chronic. Further, in chronically injured animal models, increased alpha-1 adrenergic receptor expression has been noted in arteries, potentially leading to an amplified vascular response to sympathetic influx.19 The delayed response to medications we observed in chronically injured patients may also be from other causes of external blood pressure elevation such as an increased degree of other sympathetic tone generated from delayed colonic transit times20 or concomitant essential hypertension.
Related Knowledge Centers
- Adrenaline
- Asthma
- Beta Blocker
- Sympathetic Nervous System
- Catecholamine
- Hypertension
- Norepinephrine
- G Protein-Coupled Receptor
- Alpha-2 Adrenergic Receptor
- Fight-Or-Flight Response