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Naunyn-Schmiedeberg's Archives of... Oct 20226-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral...
6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β- and β/β-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β/β-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration-response curve to 6-ND (pA 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β- and β/β-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β-adrenoceptor agonist RO-363, the selective β-adrenoceptor agonist salbutamol, and the selective β-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β- and β-/β-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Antagonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Atenolol; Betaxolol; Dopamine; Epinephrine; Male; Metoprolol; Norepinephrine; Pindolol; Propranolol; Rats; Vas Deferens
PubMed: 35798982
DOI: 10.1007/s00210-022-02268-6 -
Mechanistic pathways of fibromyalgia induced by intermittent cold stress in mice is sex-dependently.Brain Research Bulletin Sep 2022Fibromyalgia results from a complex interplay of biochemical and neurobiological elements mediated sensitization of nociceptive pathways. Despite the symptoms of...
Fibromyalgia results from a complex interplay of biochemical and neurobiological elements mediated sensitization of nociceptive pathways. Despite the symptoms of fibromyalgia negatively affect the quality of life of patients, the pathophysiology of this disease remains inconclusive, which difficult the development of an appropriate treatment. The present study investigated the involvement of the serotonergic receptors, the N-methyl-D-aspartate (NMDA)/ nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway and the oxidative stress in an animal model of fibromyalgia induced by intermittent cold stress (ICS), considering the specificities of male and female Swiss mice. The ICS exposure increased mechanical and thermal sensitivities, and decreased muscle strength in mice of both sexes. Female mice exhibited a longer-lasting mechanical sensitivity than male mice exposed to ICS along with an enhancement of the Na, K-ATPase activity in the spinal cord and cerebral cortex. Conversely, an inhibition in the Na, K-ATPase and glutathione peroxidase activities accompanied by an increase in the reactive species levels in the cerebral cortex of male mice were observed. The treatment with different serotonergic antagonists (pindolol, ketanserin and ondasetron) reversed the mechanical sensitivity in mice of both sexes, after the ICS exposure. The administration of MK-801, L-arginine and methylene blue also blocked the mechanical sensitivity in female mice exposed to ICS. Except L-arginine, MK-801 and methylene blue also attenuated this nociceptive signal in male mice, after ICS exposure. In conclusion, the modulation of serotonergic receptors, the NMDA/NO/cGMP pathway, and the oxidative stress seems contribute to nociceptive behaviors induced by ICS exposure sex-dependent.
Topics: Adenosine Triphosphatases; Animals; Arginine; Cold-Shock Response; Cyclic GMP; Dizocilpine Maleate; Female; Fibromyalgia; Male; Methylene Blue; Mice; N-Methylaspartate; Nitric Oxide; Quality of Life; Receptors, N-Methyl-D-Aspartate
PubMed: 35753533
DOI: 10.1016/j.brainresbull.2022.06.005 -
Journal of Chromatographic Science Aug 2023An azobenzenediamide bridged bis(β-cyclodextrin) chiral stationary phase (AZCDP) was prepared, and its high-performance liquid chromatography performance in...
An azobenzenediamide bridged bis(β-cyclodextrin) chiral stationary phase (AZCDP) was prepared, and its high-performance liquid chromatography performance in reversed-phase and polar organic modes was evaluated by chiral probes, including triazoles, flavanones, amino acids and β-blockers. The results showed that AZCDP had strong chiral separation ability and the 40 chiral compounds were successfully resolved, of which 32 were completely separated (Rs ≥ 1.5) and the best enantioresolution was up to 3.93 within 20 min under a wide range of pH value and temperature. The separation ability of AZCDP with double cavities was significantly better than common CD-CSPs with single cavity, which was related to the synergistic inclusion effect. Compared with the previously reported stilbene (C=C)-bridged CSP, AZCDP with azobenzene (N=N)-bridged had a wider resolution range. For example, it could resolve myclobutanil, pindolol, carteolol, betaxolol, bevanolol and bitertanol, which could not be resolved before, and should be related to the fact that the flexible N=N was more compatible with the synergistic inclusion between cavities than the rigid C=C bridge group. The azobenzenediamide bridging group could also provide hydrogen bond, π-π and other sites, which was conducive to chiral separations.
PubMed: 35726164
DOI: 10.1093/chromsci/bmac050 -
Translational Psychiatry May 2022MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, combined with psychotherapy has demonstrated efficacy for the treatment of chronic...
MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, combined with psychotherapy has demonstrated efficacy for the treatment of chronic posttraumatic stress disorder (PTSD) patients. This controlled prospective study aimed to assess the bio-behavioral underpinnings of MDMA in a translational model of PTSD. Rats exposed to predator-scent stress (PSS) were subjected to a trauma-cue at day 7 shortly after single-dose MDMA injection (5 mg/kg). The elevated plus maze and acoustic startle response tests were assessed on day 14 and served for classification into behavioral response groups. Freezing response to a further trauma-reminder was assessed on Day 15. The morphological characteristics of the dentate gyrus (DG) and basolateral amygdala (BLA) were subsequently examined. Hypothalamic-pituitary-adrenal axis and 5-hydroxytryptamine involvement were evaluated using: (1) corticosterone measurements at 2 h and 4 h after MDMA treatment, (2) Lewis strain rats with blunted HPA-response and (3) pharmacological receptor-blockade. MDMA treatment was effective in attenuating stress behavioral responses only when paired with memory reactivation by a trauma-cue. The effects of the treatment on behavior were associated with a commensurate normalization of the dendritic cytoarchitecture of DG and BLA neurons. Pretreatment with RU486, Ketanserin, or Pindolol prevented the above improvement in anxiety-like behavioral responses. MDMA treatment paired with memory reactivation reduced the prevalence rate of PTSD-phenotype 14 days later and normalized the cytoarchitecture changes induced by PSS (in dendritic complexities) compared to saline control. MDMA treatment paired with a trauma-cue may modify or update the original traumatic memory trace through reconsolidation processes. These anxiolytic-like effects seem to involve the HPA axis and 5-HT systems.
Topics: Animals; Anti-Anxiety Agents; Cues; Disease Models, Animal; Hypothalamo-Hypophyseal System; N-Methyl-3,4-methylenedioxyamphetamine; Pituitary-Adrenal System; Prospective Studies; Rats; Rats, Inbred Lew; Reflex, Startle; Stress Disorders, Post-Traumatic
PubMed: 35504866
DOI: 10.1038/s41398-022-01952-8 -
Molecules (Basel, Switzerland) Mar 2022Beta adrenoblockers are a large class of drugs used to treat cardiovascular diseases, migraines, glaucoma and hyperthyroidism. Over the last couple of decades, the...
Beta adrenoblockers are a large class of drugs used to treat cardiovascular diseases, migraines, glaucoma and hyperthyroidism. Over the last couple of decades, the anticancer effects of these compounds have been extensively studied. However, the exact mechanism is still not known, and more detailed studies are required. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers were tested. The effect on cell viability was evaluated by MTT assay, and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of the EC (half-maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.
Topics: Adrenergic beta-Antagonists; Carcinoma, Non-Small-Cell Lung; Cell Line; Humans; Lung Neoplasms; Propranolol
PubMed: 35335303
DOI: 10.3390/molecules27061938 -
Journal of Clinical Psychopharmacology
PubMed: 35230053
DOI: 10.1097/JCP.0000000000001540 -
Molecules (Basel, Switzerland) Feb 2022This study demonstrates the feasibility of molecular imprinting using a functional chain transfer agent sans a functional monomer. Ethylene glycol dimethacrylate...
This study demonstrates the feasibility of molecular imprinting using a functional chain transfer agent sans a functional monomer. Ethylene glycol dimethacrylate (EGDMA)-based MIPs were synthesised in the presence of thioglycolic acid (TGA) possessing a carboxylic acid group, capable of interacting with the chosen test template ,-(±)-propranolol (PNL) and a labile S-H bond to facilitate an efficient chain transfer reaction. Quantitative H NMR measurements showed high PNL and TGA incorporation within the MIP, indicating an efficient chain transfer process and a favourable interaction between PNL and TGA. TGA-50, with the lowest amount of CTA, showed the largest imprinting effect and an imprinting factor (IF) of 2.1. The addition of MAA to the formulation improved the binding capacity of PNL to the MIP but also increased NIP binding, resulting in a slightly decreased IF of 1.5. The K for the high-affinity sites of the TGA/MAA MIP were found to be two times lower (10 ± 1 μM) than that for the high-affinity sites of the TGA-only MIPs, suggesting that the incorporation of the functional monomer MAA increases the affinity towards the PNL template. Selectivity studies, cross-reactivity as well as binary competitive and displacement assays showed the TGA-based MIPs to be highly selective towards PNL against pindolol and slightly competitive against atenolol. The morphologies of the polymers were shown to be affected by the concentration of the TGA, transforming into discrete macrospheres (from small aggregates) at a higher TGA concentration.
PubMed: 35208956
DOI: 10.3390/molecules27041162 -
Journal of the American Society For... Feb 2022Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic...
Combining solid phase microextraction (SPME) and mass spectrometry (MS) analysis has become increasingly important to many bioanalytical, environmental, and forensic applications due to its simplicity, rapid analysis, and capability of reducing matrix effects for complex samples. To further promote the adoption of SPME-MS based analysis and expand its application scope calls for efficient and convenient interfaces that couple the SPME sample handling with the efficient analyte ionization for MS. Here, we report a novel interface that integrates both the desorption and the ionization steps in one device based on the capillary vibrating sharp-edge spray ionization (cVSSI) method. We demonstrated that the cVSSI is capable of nebulizing liquid samples in a pulled-tip glass capillary with a battery powered function generator. The cVSSI device allows the insertion of a SPME probe into the spray capillary for desorption and then direct nebulization of the desorption solvent in situ. With the integrated interface, we have demonstrated rapid MS analysis of drug compounds from serum samples. Quantitative determination of various drug compounds including metoprolol, pindolol, acebutolol, oxprenolol, capecitabine, and irinotecan was achieved with good linearity ( = 0.97-0.99) and limit of detection ranging from 0.25 to 0.59 ng/mL without using a high voltage source. Only 3.5 μL of desorption solvent and 3 min desorption time were needed for the present method. Overall, we demonstrated a portable SPME-MS interface featuring high sensitivity, short analysis time, small footprint, and low cost, which makes it an attractive method for many applications requiring sample cleanup including drug compound monitoring, environmental sample analysis, and forensic sample analysis.
Topics: Carbamazepine; Equipment Design; Limit of Detection; Metoprolol; Pindolol; Sensitivity and Specificity; Serum Albumin, Bovine; Solid Phase Microextraction; Spectrometry, Mass, Electrospray Ionization
PubMed: 35040644
DOI: 10.1021/jasms.1c00305 -
International Journal of Molecular... Dec 2021Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best... (Review)
Review
Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.
Topics: Anticonvulsants; Antidepressive Agents; Antidepressive Agents, Second-Generation; Buspirone; Central Nervous System Stimulants; Depressive Disorder, Treatment-Resistant; Humans; Ketamine; Lithium
PubMed: 34884874
DOI: 10.3390/ijms222313070 -
Journal of Psychopharmacology (Oxford,... Dec 2021To compare different β-adrenoceptor antagonists for the risk of reporting nightmare.
AIM
To compare different β-adrenoceptor antagonists for the risk of reporting nightmare.
METHODS
The study involved two approaches: first, we investigated in VigiBase, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological-pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions.
RESULTS
Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19-3.61), metoprolol (1.89, 1.66-2.16), and alprenolol (1.77, 1.06-2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47-2.00 and aROR high vs. low 1.84, 95%CI 1.53-2.22). Use of moderate or high 5-HT affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04-1.43 and aROR high vs. low 2.46, 95%CI 1.93-3.13).
CONCLUSION
In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT receptor affinity.
Topics: Adrenergic beta-Antagonists; Databases, Pharmaceutical; Dreams; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacoepidemiology; Pharmacovigilance
PubMed: 34318729
DOI: 10.1177/02698811211034810