scholarly journals Olanzapine: a full and potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogenetics

2018 ◽  
Author(s):  
Mikail Weston ◽  
Teresa Kaserer ◽  
Jenna C Carpenter ◽  
Albert Snowball ◽  
Samuel Knauss ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Atypical Antipsychotic ◽  
Muscarinic Receptors ◽  
Side Effect ◽  
Clinical Translation ◽  
Designer Drugs ◽  
European Medicines Agency ◽  
Side Effect Profile ◽  
Atypical Antipsychotic Drug ◽  
Potent Agonist

AbstractDesigner receptors exclusively activated by designer drugs (DREADDs) derived from muscarinic receptors are a powerful tool to test causality in basic neuroscience, but are also potentially amenable to clinical translation. A major obstacle is however that the widely-used agonist clozapine-N-oxide undergoes conversion to clozapine, which penetrates the blood-brain barrier but has an unfavorable side effect profile. Perlapine has been reported to activate DREADDs at nanomolar concentrations, but is not approved for use in humans by the Food and Drug Administration or European Medicines Agency, limiting its translational potential. Here we report that the atypical antipsychotic drug olanzapine, widely available in various formulations, is a full and potent agonist of the human muscarinic-receptor M4-based DREADD, facilitating clinical translation of chemogenetics to treat CNS diseases.

scholarly journals Olanzapine: A potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogenetics

2019 ◽  
Vol 5 (4) ◽  
pp. eaaw1567 ◽  
Author(s):  
Mikail Weston ◽  
Teresa Kaserer ◽  
Angela Wu ◽  
Alexandre Mouravlev ◽  
Jenna C. Carpenter ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Translation ◽  
Designer Drugs ◽  
European Medicines Agency ◽  
Side Effect Profile ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Atypical Antipsychotic Drug ◽  
Potent Agonist ◽  
M4 Muscarinic Receptor

Designer receptors exclusively activated by designer drugs (DREADDs) derived from muscarinic receptors not only are a powerful tool to test causality in basic neuroscience but also are potentially amenable to clinical translation. A major obstacle, however, is that the widely used agonist clozapineN-oxide undergoes conversion to clozapine, which penetrates the blood-brain barrier but has an unfavorable side effect profile. Perlapine has been reported to activate DREADDs at nanomolar concentrations but is not approved for use in humans by the Food and Drug Administration or the European Medicines Agency, limiting its translational potential. Here, we report that the atypical antipsychotic drug olanzapine, widely available in various formulations, is a potent agonist of the human M4 muscarinic receptor-based DREADD, facilitating clinical translation of chemogenetics to treat central nervous system diseases.

Valproic Acid:

1999 ◽  
Vol 16 (2) ◽  
pp. 130-136 ◽  
Author(s):  
Sayonara Beatriz Ranciaro Fagundes
Keyword(s):  
Health Care ◽  
Valproic Acid ◽  
Antiepileptic Drug ◽  
Detailed Analysis ◽  
Side Effect ◽  
Side Effect Profile ◽  
Care Givers

Clinical pharmacologists, neurologists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug when determining which drug is best for a given patient.The purpose of this study was to investigate valproic acid with a detailed analysis of the different reports.

Long-term efficacy and safety of imiquimod 5% and fluorouracil 1% creams in medical monotherapy of complex eyelid basal cell carcinomas

2021 ◽  
pp. 112067212110356
Author(s):  
Manpreet Singh ◽  
Aditi Mehta Grewal ◽  
Himanshi Singh ◽  
Manjula Sharma ◽  
Manpreet Kaur ◽  
...  
Keyword(s):  
Basal Cell ◽  
Side Effect ◽  
The Elderly ◽  
Fixed Dose ◽  
Side Effect Profile ◽  
Efficacy And Safety ◽  
Term Efficacy ◽  
Basal Cell Carcinomas ◽  
Double Blinded

Purpose: To study the long-term efficacy and safety of local application of imiquimod 5% and fluorouracil 1% creams in complex eyelid basal cell carcinomas (BCCs). Methods: A retrospective, non-comparative study in biopsy-proven, complex (involving canthi or >50% of eyelid length) eyelid BCC patients who were medically unfit for surgical procedures. All patients were medically treated with either of the creams using fixed-dose regimens for a minimum of 3 months. All received oral vitamin C 500 mg QID for 3 months as an adjunct for collagen healing. A minimum of “post-treatment” follow-up of 12 months was observed. Results: Of total 30 patients, imiquimod 5% and fluorouracil 1% were used in 16 and 14 patients, respectively. The mean age of our patients was 70.5 years. The co-morbidities included – severe coronary artery disease using blood-thinners ( n = 19), poorly controlled diabetes ( n = 12), poorly controlled hypertension ( n = 6), on nebulization ( n = 3), and tuberculosis with pulmonary fibrosis ( n = 2). Complete clinical tumor resolution was noted in 10 and 8 patients over 12 and 16.5 weeks, respectively, in imiquimod and fluorouracil groups. Periocular skin erythema, chemical conjunctivitis, and skin depigmentation were seen in all the patients of imiquimod group. On the other hand, the local side-effect profile in fluorouracil patients was limited. Conclusion: The medical treatment of complex eyelid BCC is a useful alternative to surgery in the elderly with significant co-morbidities. It provides a promising long-term relief with a tolerable side-effect profile. A prospective, randomized, double-blinded trial would provide stronger evidence for the efficacy of these drugs.

Design of Novel Photosensitizers and Controlled Singlet Oxygen Generation for Photodynamic Therapy

2021 ◽  
Author(s):  
Esra Tanrıverdi Eçik ◽  
Onur BULUT ◽  
Hasan Hüseyin Kazan ◽  
Elif Şenkuytu ◽  
Bunyemin Cosut
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Side Effect ◽  
Side Effect Profile ◽  
High Ability ◽  
Lower Side ◽  
Oxygen Generation ◽  
Singlet Oxygen Generation ◽  
Promising Strategy

Photodynamic therapy (PDT) is a promising strategy in cancer treatment with its relatively lower side effect profile. Undoubtedly, the key component of PDT is the photosensitizers with a high ability...

scholarly journals Efficacy and Side Effect Profile of Different Formulations of Metformin: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Jane L. Tarry-Adkins ◽  
Imogen D. Grant ◽  
Susan E. Ozanne ◽  
Rebecca M. Reynolds ◽  
Catherine E. Aiken
Keyword(s):  
Systematic Review ◽  
Side Effect ◽  
Meta Analysis ◽  
Side Effect Profile
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