Age-Related Changes in Hormone Action: The Role of Hormone Receptors
Richard C. Adelman, George S. Roth in Endocrine and Neuroendocrine Mechanisms of Aging, 2017
The experimental protocol requires that helically cut thoracic aortic strips be placed in a tissue bath and made to contract with histamine or seratonin following alpha adrenergic receptor blockade by phentolamine. Isoproterenol is then administered at various concentrations and contraction measured. An important control is the use of NaNO2 as a nonspecific relaxant. When aortic strips were exposed to this agent no age difference in contraction was observed. Thus, whatever problems might be inherent in the isolation and/or culturing conditions employed, the innate ability of tissues of all ages to contract did not appear to be disturbed. Instead, age differences seem to occur at the level of the specific β-adrenergic mechanism by which contraction is elicited. This is further demonstrated by the fact that this response is blocked by propranolol, by definition a β-adrenergic antagonist. As mentioned above, it is still possible that the specific adrenergic mechanism involved in this response in old animals is more disturbed by the isolation procedure than in young, or that the effects of denervation are differentially age-altered. These possibilities are very difficult to prove, however. Moreover, the fact that responsiveness to isoproterenol has also been found to be reduced in vivo in the case of stimulated salivary gland DNA synthesis11-15 lends further support to the validity of Fleisch's conclusions.
Importance of the Microcirculation to Intestinal Secretion
T. S. Gaginella in Regulatory Mechanisms — in — Gastrointestinal Function, 2017
It was suggested during experiments in cats that a reduced Pcap could potentiate sympathetic nerve-increased fluid absorption.192 Stimulation at 2, 4, and 8 Hz increased net fluid absorption, from glucose-containing Ringer’s solution, to about the same extent in experiments where arterial blood pressure increased and flow remained relatively constant, i.e., precapillary resistance increased and Pcap remained fairly constant. In experiments where blood pressure remained constant and blood flow decreased, i.e., P capdecreased, then net fluid absorption increased with increasing stimulation frequencies and to a greater extent than when Pcap remained constant. These results were mimicked by noradrenaline and blocked with an alpha- adrenergic antagonist.
Care of opiate users: detoxification
Berry Beaumont, David Haslam in Care of Drug Users in General Practice, 2021
Clonidine was introduced as a blood pressure-lowering drug more than three decades ago but was coincidentally found to have properties that alleviated the opiate withdrawal syndrome. Lofexidine has a similar mode of action to cloni-dine but was introduced specifically as a drug to aid opiate detoxification. It has alpha-adrenergic antagonist effects and acts centrally to reduce sympathetic tone. It does not reduce craving or have any analgesic action, but eases the rhinorrhoea, epiphora, hyperaesthesia and other symptoms of opiate withdrawal. Side-effects include drowsiness and dry mouth. The most important side-effect of clonidine is hypotension, with a risk of rebound hypertension on stopping. Lofexidine, however, has markedly reduced hypotensive action and is therefore much more suited to community use. Clonidine is now rarely used.
A review on pharmacological options for the treatment of erectile dysfunction: state of the art and new strategies
Published in Expert Opinion on Pharmacotherapy, 2023
Mattia Longoni, Alessandro Bertini, Nicolò Schifano, Emanuele Zaffuto, Paolo Maggio, Rossi Piercarlo, Sara Baldini, Giulio Carcano, Gabriele Antonini, Andrea Salonia, Francesco Montorsi, Federico Dehò, Paolo Capogrosso
Phentolamine is a nonselective α-adrenergic antagonist that decreases arterial resistance and promotes vasodilatation by inhibiting smooth muscle cell contraction [75]. The commercial preparation of Bimix, approved for clinical use in some European countries, contains papaverine hydrochloride (15 mg/mL) and phentolamine mesylate (0.5 mg/mL) in 2-mL vials [61]. The combination of these two drugs has shown the same efficacy and equal rate of prolonged erection compared to PGE1 30 μg alone, whereas it caused significantly less injection pain (15% vs 35%, p < 0.05) [76]. The addition of alprostadil (Trimix) provides the highest efficacy rates, reaching up to 92% [77,78]. This three-drug combination has similar adverse effects as alprostadil monotherapy, although fibrosis is more common when a higher dose of papaverine is used (5–10%) [77]. Noteworthy, hypotension could potentially occur with higher concentrations of the compounds [53]. In a randomized clinical trial, the combination of papaverine 17.64 mg + phentolamine 0.58 mg + PGE1 5.8 μg had a twofold efficacy rate compared to PGE1 40 μg monotherapy (50% vs 22%), with very low pain (12.5% vs 22%) due to the reduced dose of alprostadil being used [79]. Therefore, Trimix could be a suitable option for patients who underwent radical pelvic surgery as pain or tenderness after PGE1 is accentuated by an underlying cavernous nerve injury [53,63]. Unfortunately, no commercially marketed preparation for Trimix is available, due to the low stability of the combined agents.
Examination of the role of adrenergic receptor stimulation in the sensitization of neuroinflammatory-based depressive-like behavior in isolated Guinea pig pups
Published in Stress, 2023
Rachel R. Kessler, Patricia A. Schiml, Sean M. McGraw, Erin N. Tomlin, Mikayla J. Hoeferlin, Terrence Deak, Michael B. Hennessy
Experiment 2 used a strategy similar to that of Wohleb et al. (2011), in which we administered the beta-adrenergic antagonist propranolol prior to an initial isolation to determine whether enhanced sympathetic activity was necessary for the emergence of depressive-like behavior and fever during the first isolation, or the sensitization of these responses during repeated isolations. Vocalizing was also of interest in Experiment 2. Because the ability to reduce the vocalizations of isolated guinea pig pups is a well-established screen for anxiolytic medications (Borsini et al., 2002; Groenink et al., 2015), and sympathetic activity is known to contribute to anxiety (Roth et al., 2008; Holwerda et al., 2018), we expected vocalizing to be reduced following propranolol administration.
Triple reuptake inhibitors (TRIs): do they promise us a rose garden?
Published in Psychiatry and Clinical Psychopharmacology, 2018
Most current antidepressants selectively target monoamines serotonin, norepinephrine, or dopamine, which was linked to deficiencies in neurotransmission in the brains of depressed individuals while having limited effects on muscarinic and histamine receptors [2]. Other antidepressants which enhance norepinephrine and serotonin neurotransmission via other mechanisms have also been developed. These medications include mirtazepine (presynaptic alpha-2 adrenergic antagonist), as well as trazodone and nefazodone (primarily presynaptic and postsynaptic 5-HT2 antagonists). Over the years, although the data indicated the important role of mesolimbic dopamine in moderating motivation and reward-related behaviour which are typically disrupted in depression; dopamine transmission was given less attention in the management of depression [3]. Similarly, antidepressants which have been shown to sensitize mesolimbic dopamine receptors, have led to the hypothesis that enhancing synaptic dopamine availability might lead to faster antidepressant responsivity [2]. One of the major problems with current antidepressants is that almost 50% of depressed patients fail to achieve remission with their first-line antidepressant use. Another major issue with the current antidepressants is the fact that their slower onset of action with several weeks or months of treatment before any clinical improvements has been observed and reported. Therefore, a clear unmet pharmacological need for better, faster, and stronger antidepressants that have a mechanism of action beyond of serotonergic and noradrenergic neurotransmission enhancement is evident.
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