- Salts of Amoxapine with Improved Solubility for Enhanced Pharmaceutical Applicability. [Journal Article]
- AOACS Omega 2018 Feb 28; 3(2):2406-2416
- The objective of pharmaceutical cocrystallization is to create crystalline analogues that have vastly different properties, such as solubility, melting point, stability, and bioavailability from that...
The objective of pharmaceutical cocrystallization is to create crystalline analogues that have vastly different properties, such as solubility, melting point, stability, and bioavailability from that observed in the pure active pharmaceutical ingredients (APIs). Amoxapine is a benzoxazepine derivative and exhibits antidepressant properties. Amoxapine has very low solubility in water, so it was cocrystallized with natural acids in a 1:1 ratio in appropriate solvents by the solvent-drop grinding method. Single crystals of cocrystals were grown by the solvent evaporation method in water, ethanol, and methanol. Crystal structures of API salts were determined by single-crystal X-ray diffraction. Salts were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. Solubility of salts was determined in water by the shake-flask method at 37 °C using UV-vis spectroscopy. Salts of amoxapine with different acids were successfully developed, and their crystal structure was determined. Enhanced solubility was found in the salts of amoxapine for pharmaceutical application in drug formulation.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Because no information is available on the use of amoxapine during breastfeeding, another drug may be preferred, especially while nursing a newborn or preterm infant. If amoxapine is required by the ...
Because no information is available on the use of amoxapine during breastfeeding, another drug may be preferred, especially while nursing a newborn or preterm infant. If amoxapine is required by the mother, it is not a reason to discontinue breastfeeding. Exclusively breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern.
- Tricyclic amine antidepressants suppress β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) by repressing mRNA levels of key resistance genes. [Journal Article]
- CBChem Biol Drug Des 2018 Jun 28
- Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of recurrent infections in humans including endocarditis, pneumonia, and toxic shock syndrome. Novel therapeutics to treat MRSA...
Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of recurrent infections in humans including endocarditis, pneumonia, and toxic shock syndrome. Novel therapeutics to treat MRSA and other resistant bacteria are urgently needed. Adjuvant therapy, which uses a non-toxic compound to repotentiate the toxic effects of an existing antibiotic, is an attractive response to the growing resistance crisis. Herein, we describe the evaluation of structurally related, FDA-approved tricyclic amine antidepressants that selectively repotentiate MRSA to β-lactam antibiotics. Our results identify important structural features of the tricyclic amine class for β-lactam adjuvant activity. Furthermore, we describe the mechanism of action for our lead compound, amoxapine, and illustrate that it represses the mRNA levels of key β-lactam resistance genes in response to β-lactam treatment. This work is novel in that it highlights an important class of small molecules with the ability to simultaneously inhibit production of both β-lactamase and penicillin binding protein 2a.
- [Antidepressive agents and hyponatremia: A literature review and a case/non-case study in the French Pharmacovigilance database]. [Journal Article]
- TTherapie 2018 Mar 01
- CONCLUSIONS: This study suggests to stay alert to electrolyte disorders when using all antidepressants, not only serotonin reuptake inhibitors.
- A mitochondria-selective near-infrared-emitting fluorescent dye for cellular imaging studies. [Journal Article]
- BMBioorg Med Chem Lett 2018 Jun 15; 28(11):2013-2017
- This communication details the synthesis, evaluation of photophysical properties, and cellular imaging studies of cyanine chromophore based fluorescent dye 1 as a selective imaging agent for mitochon...
This communication details the synthesis, evaluation of photophysical properties, and cellular imaging studies of cyanine chromophore based fluorescent dye 1 as a selective imaging agent for mitochondria.
- NEW METHODOLOGY FOR DEVELOPMENT OF ORODISPERSIBLE TABLETS USING HIGH-SHEAR GRANULATION PROCESS. [Journal Article]
- APActa Pol Pharm 2017; 74(3):969-981
- Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granu...
Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granulation process as a new methodology for development of orodispersible tablets of high quality attributes using design of experiment approach. A two factor, three levels (32), full factorial design was carried out to investigate the main and interaction effects of independent variables, water amount (XI) and granulation time (X2) on the characteristics of granules and final product, tablet. The produced granules were analyzed for their granule size, density and flowability. Furthermore, the produced tablets were tested for: weight variation, breaking force/ crushing strength, friability, disintegration time and drug dissolution. Regression analysis results of multiple linear models showed a high correlation between the adjusted R-squared and predicted R-squared for all granules and tablets characteristics, the difference is less than 0.2. All dependent responses of granules and tablets were found to be impacted significantly (p < 0.05) by the two independent variables. However, water amount demonstrated the most dominant effect for all granules and tablet characteristics as shown by higher its coefficient estimate for all selected responses. Numerical optimization using desirability function was performed to optimize the variables under study to provide orodispersible system within the USP limit with respect of mechanical properties and disintegration time. It was found that the higher desirability (0.915) could be attained at the low level pf water (180 g) and short granulation time (1.65 min). Eventually, this study provides the formulator with helpful information in selecting the proper level of water and granulation time to provide an orodispersible system of high crushing strength and very low disintegration time, when high shear granulation methodology was used as a method of manufacture.
- Resensitization of methicillin-resistant Staphylococcus aureus by amoxapine, an FDA-approved antidepressant. [Journal Article]
- HHeliyon 2018; 4(1):e00501
- The rapid increase in bacterial resistance to antibiotics is a global healthcare crisis. Non-antibiotic pharmaceuticals that have attained approval by the United States Food and Drug Administration h...
The rapid increase in bacterial resistance to antibiotics is a global healthcare crisis. Non-antibiotic pharmaceuticals that have attained approval by the United States Food and Drug Administration have the potential to be repurposed as bacterial resistance-modifying agents and therefore could become valuable resources in our battle against antibiotic-resistant microbes. Amoxapine is a tetracyclic antidepressant used in the treatment of major depressive disorder. Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and broth microdilution assays. Amoxapine also reduced the bacterial cleavage of nitrocefin in a dose-dependent manner, suggesting that it may exert its adjuvant effects through reduction of beta-lactamase activity.
- Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants. [Journal Article]
- MNMol Neuropsychiatry 2017; 3(2):97-107
- Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms ref...
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes in Caenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail to forage and will remain in place for >12 days or until they die. Their immobility can be prevented with drugs used to treat depression and schizophrenia and that reduce immobility in the forced swimming test. This includes amitriptyline, amoxapine, clozapine, and olanzapine, but not benzodiazepines and haloperidol. Recovery experiments confirm that immobility is induced and maintained by excessive signaling via serotonergic and muscarinic cholinergic pathways. The immobility response described here represents a potential protophenotype for avolition/anhedonia in man. This work may provide clues about why there is a significant increase in depression in patients with diabetes and suggest new therapeutic pathways for disorders featuring diminished motivation as a prominent symptom.
- Combating Multidrug-Resistant Pathogens with Host-Directed Nonantibiotic Therapeutics. [Journal Article]
- AAAntimicrob Agents Chemother 2018; 62(1)
- Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), i...
Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an in vitro murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral Clostridium difficile infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with Klebsiella pneumoniae when it was administered at the time of infection or at 24 h postinfection. Using the same in vitro cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against K. pneumoniae For Acinetobacter baumannii, 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three A. baumannii strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new therapeutics to combat multidrug-resistant pathogens of public health concern.
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- Specific Patient Features Affect Antiepileptic Drug Therapy Decisions: Focus on Gender, Age, and Psychiatric Comorbidities. [Journal Article]
- CPCurr Pharm Des 2017; 23(37):5639-5648
- CONCLUSIONS: A careful evaluation of the patient variables analysed in the present review is useful to personalize and optimize AED therapy.