-
Journal of the Neurological Sciences Jan 2017To describe improvement in blepharospasm with apraclonidine.
OBJECTIVE
To describe improvement in blepharospasm with apraclonidine.
BACKGROUND
Blepharospasm is a focal dystonia involving chiefly the orbicularis oculi and periocular muscles resulting in involuntary sustained eyelid closure. Botulinum toxin injection is the mainstay of treatment with meaningful improvement in over 85% of patients, but the effects often wear off within 3-4months. Apraclonidine is an alpha-2 adrenergic receptor agonist, which causes contraction of superior tarsal (Müller) muscle which may improve blepharospasm-related eyelid closure. We propose that apraclonidine may be a useful short-term treatment in patients with blepharospasm, particularly during wearing off from botulinum toxin injection.
METHODS
Patients who had pre-mature wearing off of botulinum injection effect were evaluated before and after the administration of 2 drops of apraclonidine 0.5%-1% solution to each eye. Subjective patient impressions and examiner's impression of symptoms pre and post-apraclonidine administration were recorded. A blinded rater evaluated the videos and provided an independent assessment of the severity of symptoms pre- and post-administration, using a 0-4 scale.
RESULTS
Our study included 7 patients (4 male) with a mean age of 61years and mean duration of blepharospasm of 3.6years. There was a subjective, albeit transient (about 2-4h) improvement in blepharospasm reported by all patients and by the examiner. The mean severity scores, based on blinded video ratings, showed a reduction from of 3.4 pre-administration to 2.3 post-administration of apraclonidine (p<0.025). No adverse effects were noted.
CONCLUSIONS
Apraclonidine is a potentially useful medication for short term management of blepharospasm symptoms while awaiting botulinum toxin injection.
Topics: Adrenergic alpha-2 Receptor Agonists; Aged; Blepharospasm; Botulinum Toxins; Clonidine; Female; Humans; Male; Middle Aged; Neurotoxins
PubMed: 28017248
DOI: 10.1016/j.jns.2016.11.029 -
The Western Journal of Emergency... May 2015
Topics: Adrenergic Agonists; Anaphylaxis; Community Medicine; Epinephrine; First Aid; Humans; Injections, Intramuscular; Schools; Severity of Illness Index; Time Factors
PubMed: 25987911
DOI: 10.5811/westjem.2015.3.25337 -
The Veterinary Clinics of North... Nov 2015Glaucoma is a painful and often blinding group of ocular diseases for which there is no cure. Although the definition of glaucoma is rapidly evolving, elevated... (Review)
Review
Glaucoma is a painful and often blinding group of ocular diseases for which there is no cure. Although the definition of glaucoma is rapidly evolving, elevated intraocular pressure (IOP) remains the most consistent risk factor of glaucoma in the canine patient. Therapy should be aimed at neuroprotection. The mainstay of therapy focuses on reducing IOP and maintaining a visual and comfortable eye. This article discusses the most current ocular hypotensive agents, focusing on their basic pharmacology, efficacy at lowering IOP, and recommended use in the treatment of idiopathic canine glaucoma.
Topics: Adrenergic Agonists; Animals; Carbonic Anhydrase Inhibitors; Cholinergic Agonists; Dog Diseases; Dogs; Drug Delivery Systems; Gasotransmitters; Glaucoma; Miotics; Prostaglandins; rho-Associated Kinases
PubMed: 26319445
DOI: 10.1016/j.cvsm.2015.06.004 -
Biochemical and Biophysical Research... Jun 2022The β-adrenergic receptor (βAR) is the most essential drug target for overactive bladder and has therapeutic potentials for the treatments of type 2 diabetes and...
The β-adrenergic receptor (βAR) is the most essential drug target for overactive bladder and has therapeutic potentials for the treatments of type 2 diabetes and obesity. Here, we report the cryo-electron microscopy structures of the βAR-G signaling complexes with the selective agonist, solabegron and the nonselective agonist, isoproterenol. Comparison of the isoproterenol-, mirabegron-, and solabegron-bound βAR structures revealed that the extracellular loop 2 changes its conformation depending on the bound agonist and plays an essential role in solabegron binding. Moreover, βAR has an intrinsically narrow exosite, regardless of the agonist type. This structural feature clearly explains why βAR prefers mirabegron and solabegron, as the narrow exosite is suitable for binding with agonists with elongated shapes. Our study deepens the understanding of the binding characteristics of βAR agonists and may pave the way for developing βAR-selective drugs.
Topics: Adrenergic beta-3 Receptor Agonists; Aniline Compounds; Benzoates; Biphenyl Compounds; Cryoelectron Microscopy; Diabetes Mellitus, Type 2; Humans; Isoproterenol; Receptors, Adrenergic, beta-3
PubMed: 35489202
DOI: 10.1016/j.bbrc.2022.04.065 -
British Journal of Pharmacology Jul 2019β -Adrenoceptor agonists have proven useful in the treatment of overactive bladder syndrome, but it is not known whether their efficacy during chronic administration... (Review)
Review
β -Adrenoceptor agonists have proven useful in the treatment of overactive bladder syndrome, but it is not known whether their efficacy during chronic administration may be limited by receptor-induced desensitisation. Whereas the β -adrenoceptor has phosphorylation sites that are important for desensitisation, the β -adrenoceptor lacks these; therefore, it had been assumed that β -adrenoceptors are largely resistant to agonist-induced desensitisation. While all direct comparative studies demonstrate that β -adrenoceptors are less susceptible to desensitisation than β -adrenoceptors, desensitisation of β -adrenoceptors has been observed in many models and treatment settings. Chimeric β - and β -adrenoceptors have demonstrated that the C-terminal tail of the receptor plays an important role in the relative resistance to desensitisation but is not the only relevant factor. While the evidence from some models, such as transfected CHO cells, is inconsistent, it appears that desensitisation is observed more often after long-term (hours to days) than short-term (minutes to hours) agonist exposure. When it occurs, desensitisation of β -adrenoceptors can involve multiple levels including down-regulation of its mRNA and the receptor protein and alterations in post-receptor signalling events. The relative contributions of these mechanistic factors apparently depend on the cell type under investigation. Which if any of these factors is applicable to the human urinary bladder remains to be determined. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
Topics: Adrenergic beta-3 Receptor Agonists; Animals; Humans; Receptors, Adrenergic, beta-3
PubMed: 30809805
DOI: 10.1111/bph.14633 -
Anesthesia and Analgesia Dec 2023The hypothesis "General anesthesia consists of producing both loss of consciousness and the inhibition of noxious stimuli reaching the brain and causing arousal" was... (Review)
Review
The hypothesis "General anesthesia consists of producing both loss of consciousness and the inhibition of noxious stimuli reaching the brain and causing arousal" was used as a basis for the review of published data on general anesthetic interactions with antinociceptive agents: opioids, α 2 adrenergic agonists, and systemic sodium channel blockers. This review is focused on a specific type of anesthetic interaction-the transformation of antinociceptive agents into general anesthetic adjuncts. The primary aim is to answer 2 questions. First, how does an antinociceptive agent transform the effect of an anesthetic in providing a certain component of anesthesia-hypnosis, immobility, or hemodynamic response to noxious stimulation? Second, does a combination of an anesthetic with an adjunct result in a simple summation of their respective effects or in a supra-additive or infra-additive interaction? The Medline database was searched for data describing the interactions of antinociceptive agents and general anesthetics. The following classes of antinociceptive agents were considered: opioids, α 2 adrenergic agonists, and systemic sodium channel blockers. Drugs used in combination with antinociceptive agents were general anesthetics and benzodiazepines. The following terms related to drug interactions were used: anesthetic interactions, synergy, antagonism, isobolographic analysis, response surface analysis, and fractional analysis. The interactions of antinociceptive agents with general anesthetics result in a decrease of general anesthetic requirements, which differ for each of the components of general anesthesia: hypnosis, immobility, and hemodynamic response to noxious stimulation. Most studies of the nature of anesthetic interactions are related to opioid-general anesthetic combinations, and their conclusions usually confirm supra-additivity.
Topics: Analgesics; Analgesics, Opioid; Drug Interactions; Anesthetics, General; Sodium Channel Blockers; Adrenergic Agonists; Dose-Response Relationship, Drug
PubMed: 37851902
DOI: 10.1213/ANE.0000000000006737 -
JAMA Network Open Oct 2023Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero...
IMPORTANCE
Corticosteroids and β2-adrenergic agonists are commonly used during pregnancy to treat asthma. However, offspring neurodevelopmental outcomes following in utero exposure to these medications remain unclear.
OBJECTIVE
To investigate the association between timing of in utero exposure to corticosteroids and β2-adrenergic agonists and offspring neurodevelopmental milestones during the first 3 years of life.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study obtained data from the Japan Environment and Children's Study, an ongoing birth cohort study conducted in collaboration with 15 Regional Centers across Japan. Participants were mother-offspring pairs who were recruited between January 1, 2011, and March 31, 2014. Data were analyzed between January and February 2023.
EXPOSURE
Corticosteroids and β2-adrenergic agonists were the exposure of interest. Timing of corticosteroid and β2-adrenergic agonist exposure included early pregnancy (weeks 0-12), mid- to late pregnancy (weeks >12), and both stages of pregnancy.
MAIN OUTCOMES AND MEASURES
Offspring neurodevelopmental milestones (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition, at 6, 12, 18, 24, 30, and 36 months.
RESULTS
In total, 91 460 mother-offspring pairs were analyzed. Among mothers, the mean (SD) age at delivery was 31.20 (5.05) years. Among offspring, 46 596 (50.9%) were males and 44 864 (49.1%) were females, of whom 66.4% had a gestational age of 39 to 41 weeks. During early, mid- to late, and both stages of pregnancy, 401 (0.4%), 935 (1.0%), and 568 (0.6%) offspring, respectively, were exposed to corticosteroids, whereas 170 (0.2%), 394 (0.4%), and 184 (0.2%), respectively, were exposed to β2-adrenergic agonists. No association of corticosteroid exposure during early, mid- to late, and both stages of pregnancy with all 5 neurodevelopmental milestones was found. Similarly, no association between β2-adrenergic agonist use during early pregnancy and all 5 neurodevelopmental milestones was observed. An association was found between β2-adrenergic agonist exposure during mid- to late pregnancy and delayed personal-social skills (adjusted odds ratio, 1.48; 95% CI, 1.01-2.32; P = .045).
CONCLUSIONS AND RELEVANCE
Results of this study found no association between in utero corticosteroid and β2-adrenergic agonist exposure and offspring neurodevelopmental outcomes, regardless of the timing of exposure. Despite the limitations and low power of the study, the findings suggest that corticosteroids and β2-adrenergic agonists are safe for pregnant individuals with asthma and the neurodevelopment of their offspring.
Topics: Male; Child; Female; Humans; Pregnancy; Adult; Infant; Cohort Studies; Adrenergic Agonists; Prenatal Exposure Delayed Effects; Asthma; Adrenal Cortex Hormones
PubMed: 37874567
DOI: 10.1001/jamanetworkopen.2023.39347 -
British Journal of Pharmacology Jul 2019Neuropathic pain can arise from disease or damage to the nervous system. The most common symptoms of neuropathic pain include spontaneous pain, allodynia, and... (Review)
Review
Neuropathic pain can arise from disease or damage to the nervous system. The most common symptoms of neuropathic pain include spontaneous pain, allodynia, and hyperalgesia. There is still limited knowledge about the factors that initiate and maintain neuropathic pain. However, ample evidence has proved the antinociceptive role of spinal α-adrenoceptors following nerve injury. It is well-documented that noradrenergic descending pathways from supraspinal loci exert an inhibitory influence on the spinal cord nociceptive neurons, mostly through the activation of spinal α -adrenoceptors. This, in turn, suppresses transmission of pain input and the hyperexcitability of spinal dorsal horn neurons. There is considerable evidence demonstrating that spinal application of α -adrenoceptor agonists leads to analgesic effects in animal models of neuropathic pain. Today, despite the recent rapid development of neuroscience and drug discovery, effective drugs with clear basic mechanisms have remained a mystery. Here, we give an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α -adrenoceptors in the spinal dorsal horn. We then suggest that α -adrenoceptor agonist may be useful to treat neuropathic pain. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
Topics: Adrenergic Agonists; Animals; Humans; Neuralgia; Receptors, Adrenergic, alpha-2; Spine
PubMed: 30657594
DOI: 10.1111/bph.14580 -
Lower Urinary Tract Symptoms Mar 2023Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and...
OBJECTIVES
Goto-Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M -muscarinic receptor antagonist and a β -adrenergic receptor agonist.
METHODS
Ten-week-old female GK rats were fed a high-fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle, the M -muscarinic receptor antagonist solifenacin, the β -adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M -muscarinic and β -adrenergic receptors were investigated.
RESULTS
After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle-, solifenacin-, or mirabegron-treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M -muscarinic and β -adrenergic receptors were detected, the expression of M -muscarinic receptor mRNA was significantly higher than that of β -adrenergic receptor mRNA.
CONCLUSIONS
The cold stress-induced bladder overactivity was not improved by either the M -muscarinic receptor antagonist or the β -adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M -muscarinic antagonists and β -adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.
Topics: Rats; Female; Animals; Urinary Bladder; Muscarinic Antagonists; Solifenacin Succinate; Urinary Bladder, Overactive; Cold-Shock Response; Diabetes Mellitus, Type 2; Adrenergic Agonists; Quality of Life; Receptors, Muscarinic; RNA, Messenger; Receptors, Adrenergic; Adrenergic beta-3 Receptor Agonists
PubMed: 36543093
DOI: 10.1111/luts.12472 -
Hormones (Athens, Greece) Jun 2022Obesity is a chronic condition of multifactorial etiology characterized by excessive body fat due to a calorie intake higher than energy expenditure. Given the intrinsic... (Review)
Review
Obesity is a chronic condition of multifactorial etiology characterized by excessive body fat due to a calorie intake higher than energy expenditure. Given the intrinsic limitations of surgical interventions and the difficulties associated with lifestyle changes, pharmacological manipulation is currently one of the main therapies for metabolic diseases. Approaches aiming to promote energy expenditure through induction of thermogenesis have been explored and, in this context, brown adipose tissue (BAT) activation and browning have been shown to be promising strategies. Although such processes are physiologically stimulated by the sympathetic nervous system, not all situations that are known to increase adrenergic signaling promote a concomitant increase in BAT activation or browning in humans. Thus, a better understanding of factors involved in the thermogenesis attributed to these tissues is needed to enable the development of future therapies against obesity. Herein we carry out a critical review of original articles in humans under conditions previously known to trigger adrenergic responses-namely, cold, catecholamine-secreting tumor (pheochromocytoma and paraganglioma), burn injury, and adrenergic agonists-and discuss which of them are associated with increased BAT activation and browning. BAT is clearly stimulated in individuals exposed to cold or treated with high doses of the β3-adrenergic agonist mirabegron, whereas browning is certainly induced in patients after burn injury or with pheochromocytoma, as well as in individuals treated with β3-adrenergic agonist mirabegron for at least 10 weeks. Given the potential effect of increasing energy expenditure, adrenergic stimuli are promising strategies in the treatment of metabolic diseases.
Topics: Adipose Tissue, Brown; Adrenal Gland Neoplasms; Adrenergic Agents; Adrenergic Agonists; Energy Metabolism; Humans; Nervous System; Obesity; Pheochromocytoma
PubMed: 35247188
DOI: 10.1007/s42000-022-00361-2