Does Prozac increase glutamate? (3+ clinical evidence)
By
Dr Maryam Shabbir (PhD)
| Reviewed by
Ivan Kahwa
The contents of this article are fact-based except otherwise stated within the article.
Author bio
Dr Maryam Shabbir PhD is a pharmacist with expertise in drugs delivery, pharmacology, dosage form design, transdermal drug delivery system, microneedles, and solubility enhancement. She writes and reviews content on these topics.
Dr Maryam Shabbir’s Highlights:
Assistant Professor at The University of Lahore, Lahore, Pakistan.
PhD in Pharmaceutics with a focus on solubility enhancement of BCS class II and III drugs and their delivery through transdermal route using microneedles.
Doctor of Pharmacy at the University of Lahore with a two-year scholarship.
Professional Experience:
Dr Maryam Shabbir joined Faculty of Pharmacy, The University of Lahore as soon as she completed her Pharm-D in 2010. In 2017, she got promoted as an assistant professor.
Dr Maryam Shabbir has supervised twenty two M.Phil. students in pharmaceutics in areas such as transdermal drug delivery system, nanoparticles, microparticle, solid dispersion, and transdermal patches.
Dr Maryam Shabbir has also contributed to several business consultancies and research projects, including the development of lyophilized wafer of Acyclovir with Medisearch Pharmacal Pvt. Ltd., a major pharmaceutical industry in Pakistan.She has also worked as a team member in one of the Contract Research Organizations of Pakistan.
Dr Maryam Shabbir has organized two International conferences and three national conferences as conference secretary for the University of Lahore in collaboration with Punjab Higher Education Commission of Pakistan.
Dr Maryam Shabbir has submitted two patents to the Intellectual Property Organization of Pakistan (IPO), and three patents are in pipeline. She has also presented her work in different exhibitions organized by the Higher Education Commission of Pakistan. She works in close liaison with the Innovation Hub, University of Lahore, Pakistan.
Dr Maryam Shabbir participated as a member of the examination board for several Master’s exams and as an external examiner for Pharm-D in reputable universities of Pakistan. She is also a member of Punjab Pharmacy Council and Pakistan Pharmacist Association.
Education:
2010 Pharm D at the University of Lahore, Lahore, Pakistan
2013 Master of Philosophy (Pharmaceutics) at the University of Lahore, Lahore, Pakistan
2022 PhD (Pharmaceutics) at the University of Lahore, Lahore, Pakistan
The main publications of Dr. Maryam Shabbir are:
Saeed S, Barkat K, Ashraf MU, Shabbir M, Anjum I, Badshah SF, et al. Flexible Topical Hydrogel Patch Loaded with Antimicrobial Drug for Accelerated Wound Healing. Gels. 2023;9(7):567.
Arshad J, Barkat K, Ashraf MU, Badshah SF, Ahmad Z, Anjum I, Shabbir M, et al. Preparation and characterization of polymeric cross-linked hydrogel patch for topical delivery of gentamicin. e-Polymers. 2023;23(1):20230045.
Arshad J, Barkat K, Ashraf MU, Badshah SF, Ahmad Z, Anjum I, Shabbir M, Mehmood Y, Khalid I, Malik NS, Bin Jardan YAl. Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study. Drug Development and Industrial Pharmacy. 2022;48(11):611-22.
Maher S, Shabbir M, Anam I, Khan N, Iqbal S, Saleem F. Anti-inflammatory and anti-oxidant activities of methanolic extract of medicinal plants from Balochistan. Int J Biol Biotechnol. 2020;15:691-7.
Shabbir M, Sajid A, Hamid I, Sharif A, Akhtar MF, Raza M, et al. Influence of different formulation variables on the performance of transdermal drug delivery system containing tizanidine hydrochloride: in vitro and ex vivo evaluations. Brazilian Journal of Pharmaceutical Sciences. 2019;54:e00130.
Nagra U, Adnan S, Shafqat S, Shabbir M, Ali S, Zafar A, et al. Effect of Sustained Release Polymers on Drug Release Profile of Aceclofenac Tablets Physicochemical Properties, Analysis of Kinetics and Fit Factor. Indian J Pharm Educ Res. 2019;53:58-65.
Fatima S, Akhtar MF, Ashraf KM, Sharif A, Saleem A, Akhtar B, Peerzada S, Shabbir M, Ali S, Ashraf W, Antioxidant and alpha amylase inhibitory activities of Fumaria officinalis and its antidiabetic potential against alloxan induced diabetes. Cellular and molecular biology (Noisy-le-Grand, France). 2019;65(2):50-7.
Saeed S, Raza M, Shabbir M, Akhtar MF, Sharif A, Zaman M, et al. Study of Multi-Drug Resistance Associated with Anti-Tuberculosis Treatment by DOT Implementation Strategy in Pakistan. Journal of Basic & Applied Sciences. 2018;14:107-12.
Arshad I, Ali S, Amin U, Shabbir M, Raza M, Sharif A, et al. Effect of hydrophilic and hydrophobic polymer on the release of ketoprofen and allopurinol from bilayer matrix transdermal patch. Advances in Polymer Technology. 2018;37(8):3076-83.
Sohail K, Javaid Z, Hamid I, Sharif A, Akhtar MF, Raza M, Ali S, Shabbir M, Peerzada S, Ahmad S. Formulation and evaluation of ranitidine floating tablets using different polymer combinations. Journal of Toxicological &Pharmaceutical Sciences. 2017;1(1):18-25.
Sharif A, Akhtar MF, Akhtar B, Saleem A, Manan M, Shabbir M, et al. Genotoxic and cytotoxic potential of whole plant extracts of Kalanchoe laciniata by Ames and MTT assay. EXCLI journal. 2017;16:593.
Shahid N, Adnan S, Farooq M, Ali S, Shabbir M, Masood Z, et al. Development of compressed coated polypill with mucoadhesive core comprising of atorvastatin/clopidogrel/aspirin using compression coating technique. Acta Poloniae Pharmaceutica. 2017;74(2):477-87.
Shabbir M, Fazli AR, Ali S, Raza M, Sharif A, Akhtar MF, et al. Effect of hydrophilic and hydrophobic polymer on in vitro dissolution and permeation of bisoprolol fumarate through transdermal patch. Acta Pol Pharm. 2017;74:187-97.
Saba Mazhar NS, Raza M, Akhtar B, Zahra A, Akhtar MF, Saleem A, Chishti SA, Shabbir M, Sharif A. A descriptive study of Measles outbreak in Lahore, Pakistan in 2013. J Toxicol Pharmaceut Sci. 2017;1(1):26-30.
Manzoor I, Raza M, Shabbir M, Ali S, Akhtar MF, Peerzada S, et al. Formulation and characterization of curcumin nanoparticles prepared from eudragit L-100 and poly vinyl alcohol as polymer. J Toxicol Pharmaceut Sci. 2017;1(1):7-12.
Akhtar MF, Sharif A, Saleem M, Saleem A, Akhtar B, Raza M, Ijaz H, Shabbir M, Ali S, Nasim MB, Peerzada S. Genotoxic and cytotoxic potential of Alternanthera Bettzickiana, an important ethno-medicinal plant. Cellular and Molecular Biology. 2017;63(8):109-14.
Ahmed S, Saeed-Ul-Hassan S, Islam M, Qureshi F, Waheed I, Munawar I, Ishtiaq S, Rasool S, Akhtar MF, Chishti SA, Shabbir M. Anti-oxidant activity of Pistachia khinjuk supported by phytochemical investigation. Acta Pol Pharm. 2017;74(1):173-8.
Shahid N, Ali S, Shabbir M, Waqar K. Compressed coated polypill with mucoadhesive core for cardiovascular disease-A review. The Pharma Innovation. 2016;4(3, Part B).
Shabbir M, Ali S, Farooq M, Adnan S, Yousaf M, Idrees A, et al. Formulation factors affecting in vitro and ex vivo permeation of bisoprolol fumarate from a matrix transdermal patch. Advances in Polymer Technology. 2016;35(3):237-47.
Mehmood A, Hamid I, Sharif A, Akhtar MF, Akhtar B, Saleem A, Shabbir M, et al. Evaluation of anti-inflammatory, analgesic and antipyretic activities of aqueous and ethanolic extracts of seeds of Buchanania lanzan Spreng. In animal models. Acta poloniae pharmaceutica. 2016;73(6):1601-8.
Ali S, Shabbir M, Shahid N, Amin U, Hamid I, Raza M. Effect of Polysorbate 80 Through Rabbit’s Skin Using Transdermal Patch Loaded with Bisoprolol Fumarate as Model Drug. Pakistan J Zool. 2016;48(1):227-34.
Akhtar MF, Saleem A, Sharif A, Akhtar B, Nasim MB, Peerzada S, Raza M, Ijaz H, Ahmed S, Shabbir M, Ali S. Genotoxic and cytotoxic action potential of Terminalia citrina, a medicinal plant of ethnopharmacological significance. EXCLI journal. 2016;15:589.
Ali S, Shabbir M, Shahid N. The Structure of Skin and Transdermal Drug Delivery System-A Review. Research Journal of Pharmacy and Technology. 2015;8(2):103-9.
Shabbir M, Ali S, Shahid N, Rehman K, Amin U, Raza M. Formulation considerations and factors affecting transdermal drug delivery system-A review. International Journal of Pharmacy and Integrated Life Sciences. 2014;2(9):20-35.
Ali S, Shabbir M, Farooq M, Adnan S, Shahid N. The enhancement effect of permeation enhancers on Bisoprolol fumarate across animal membrane using Franz diffusion cell. Research Journal of Pharmacy and Technology. 2014;7(12):1391-5.
Conference papers
Shabbir M (2022), Sustainable Development Goals (SDGs): A Policy Gap between Health and Pharmaceutical Industry. In International Social Science Conference 2022 (School of International Social Sciences, University of Lahore).
Shabbir M (2022), Controlling Permeation of Ketoprofen and Allopurinol through Bilayer Transdermal Patch using Multiple Pharmaceutical Ingredients. In Current Advancement in Pharmacy Practice (CAPP)- Theory to Practice (University of Lahore, Lahore)
Shabbir M (2018), Nanocarriers Mediated Photodynamic Therapy for the Treatment of Different Cancers. In the 4th Annual International Pharmacy Scientific Symposium and Poster Exhibition-2018 (University of Central Punjab, Lahore).
Shabbir M (2018), Lipid Enveloped Polymeric Nanoparticles for Targeted Photodynamic Chemotherapy. In the 3rd International Health Trigon Summit-2018 (University of Lahore).
You can view some of Dr Maryam’s work below and links to her professional profile.
Publon Profile: publons.com/researcher/1495244/maryam-shabbir
ORCID: 0000-0002-9308-5175
Researchgate: https://www.researchgate.net/profile/Maryam-Shabbir-4
Google Scholar: Maryam Shabbir – Google Scholar
Linkedin Profile: https://www.linkedin.com/in/maryam-shabbir-b409a270
Reviewer bio
Mr Ivan Kahwa is a chemist and phytopharmaceutical scientist with expertise in chemistry, pharmacology, phytochemistry, and Nanobiotechnology. He writes and reviews content on these topics.
Mr Ivan Kahwa’s Highlights:
Guest Researcher at the University of Leipzig, Senior Research Fellow/Scientist, and Lecturer at the Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology.
Professional Experience:
Mr Ivan joined PHARMBIOTRAC as a research fellow/scientist during his master of science tenure. He contributed to the development of most of the phytopharmaceutical products in the project. Furthermore, he participated in carrying out the pharmacological activities of the developed products in laboratory animals such as mice and rats in order to develop proper doses hence leading to pre-clinical studies.
With the above relevant research experience, Ivan started to work with the University of Leipzig on collaborative projects with Mbarara University to develop the chemistry of Ugandan Medicinal plants and their pharmacological activities. This was coupled with several consultative positions by different German NGOs. Mr. Kahwa is also a supporting in the teaching and learning at the Departments of Pharmacy and Pharmaceutical Sciences, Faculty of Medicine, Mbarara University of Science and Technology.
With the increase in antimicrobial resistance globally, Ivan retooled his thinking towards developing new naturally derived antibiotic regimens from Ugandan propolis with the assistance of nanotechnology to improve their delivery to microbial cells. Kahwa has also published over 28 articles in peer-reviewed journals and he is currently reviewing for many journals.
Education:
2023-2027: PhD in Pharmaceutical Sciences (ongoing) with a focus on Pharmaceutical Microbiology and Nanobiology at Mbarara University of Science and Technology.
2022: 2Msc. in Pharmacognosy and Natural Medicine Science at Mbarara University of Science and Technology.
2018: Bachelor of Science (Chemistry) at Mbarara University of Science and Technology.
Publications:
▪ Iqbal, S., Jabeen, F., Kahwa, I., & Omara, T. 2023. Suberosin Alleviates Thiazolidinedione-Induced Cardiomyopathy in Diabetic Rats by Inhibiting Ferroptosis via Modulation of ACSL4-LPCAT3 and PI3K-AKT Signaling Pathways. Cardiovascular Toxicology. https://doi.org/10.1007/s12012-023-09804-7
▪ Gupta, A. K., Yadav, R., Sharma, S., Sawale, J., & Kahwa, I. 2023. Anti-ageing Activity and Antioxidant Activity of Methanol Extracts of Leaves and Flowers of Salvia officinalis and Rosmarinus officinalis. Journal of Young Pharmacists, 15(3), 448–455. https://doi.org/10.5530/jyp.2023.15.60
▪ Tolo, C.U., Kahwa, I., Nuwagira, U., Weisheit, A. and Ikiriza, H., 2023. Medicinal plants used in treatment of various diseases in the Rwenzori Region, Western Uganda. Ethnobotany Research and Applications, 25, pp.1-16.
https://ethnobotanyjournal.org/index.php/era/article/view/4683
▪ Kahwa, I., Ajayi, C.O., Yadav, R., Chauhan, N.S., Shah, K., Abdelgadir, A.A., Shegena, E.A., Daniel, S., Omara, T., Asiimwe, J.B. and Ikiriza, H., 2023. Pharmacognostic and phytochemical studies as an invaluable approach for correct identification of medicinal plants: The case of Artemisia vulgaris L. substituted for Artemisia annua L. in Western Uganda. TMR Integr Med, 7, p.e23004.
https://doi.org/10.53388/TMRIM202307004
▪ Nalimu, F., Oloro, J., Kahwa, I. and Ogwang, P.E., 2021. Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox. Future Journal of Pharmaceutical Sciences, 7, pp.1-21.
https://doi.org/10.1186/s43094-021-00296-2
▪ Elamin, O.H.S., Ali, M.A., Elgezuli, I.A.A., Bashir, M.A. and Kahwa, I., 2021. Diagnosis of pre-and post-treatment of echinococcus granulosus with counter current immune electrophoresis and bacterial co-agglutination. Journal of Microbiology and Infectious Diseases, 11(02), pp.88-94.
https://doi.org/10.5799/jmid.951600
Published book Chapter
▪ Kahwa, I., Ayesiga, I., Nakalema, S., Alinaiswe, R., Mbabazi, R. and Iqbal, S., 2023. Natural products in the management of onchocerciasis. In Natural Products in Vector-Borne Disease Management (pp. 63-80). Academic Press. Book Chapter.
https://doi.org/10.1016/B978-0-323-91942-5.00012-4
Submitted manuscripts Under Review:
▪ Comparison of the Wound Healing Activity of the Leaf and Leaf Ash Extracts of Vernonia amygdalina in Rats. Journal name: Clinical Phytoscience
▪ Ethnobotanical Survey of Medicinal plants used in the management of cancer in Uganda. Journal name: Journal of Herbal Medicine
▪ Ethnobotanical survey and phytochemical screening of medicinal plants used in treatment of epilepsy by PROMETRA-Uganda Traditional Health Practitioners in Mpigi District, Uganda. Journal name: Journal of Ethnopharmacology
Submitted book chapters under review
1.Book title: Algae as a Natural Solution for Water-Food-Energy Nexus, Section 4: Microalgae and cyanobacteria for food applications, Chapter 4.6: Safety, toxicological and allergenic aspects of using algae for food. Authors: Christine Kyarimpa, Tom Omute, Caroline K. Nakiguli, Alice V. Khanakwa4, Christopher Angiro, Ivan Kahwa, Fortunate Ahumuza, Timothy Omara*. Publisher: Springer Nature Singapore Pte Ltd. 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore.
2.Book title: Nutraceuticals Inspiring the Contemporary Therapy for Lifestyle Diseases. Chapter: Nutraceutical applications of Seaweeds and their Phytocompounds in Nutrition and Treatment of Diseases. Authors: Ivan Kahwa, Timothy Omara , Innocent Ayesiga , Gael Noel Neh Neba Ambe , Zehbanaz Javidbhai Panwala , Rachel Mbabazi , Shabnoor Iqbal , Christine Kyarimpa , Christine Betty Nagawa , Kamal Shah ,Nagendra Singh Chauhan* Publisher: CRC Press
You can view my works on the following professional sites:
Research Gate: https://www.researchgate.net/profile/Ivan-Kahwa
Google Scholar: https://scholar.google.com/citations?user=tOwrvqoAAAAJ&hl=en
ORCID: https://orcid.org/0000-0002-6440-3437
Linkedin: https://de.linkedin.com/in/ivan-kahwa-865450159
In this article, we will discuss whether Prozac (fluoxetine) increases the glutamate release. Prozac is a popular SSRI (selective serotonin reuptake inhibitor) antidepressant used in the treatment of major depressive disorder (MDD), panic attacks, obsessive-compulsive disorder (OCD), and premenstrual dysphoric disorder (PMDD).
Does Prozac increase glutamate?
No, Prozac does not cause an increase in glutamate release, rather it decreases the glutamate release to induce the antidepressant effect in the patient. Prozac is known to increase the serotonin level and decrease the glutamate level and GABA.
What is the clinical evidence of Prozac’s effect on glutamate levels?
Glutamate is a free amino acid found in the brain. Glutamate transporters continuously remove glutamate from the brain’s extracellular fluid to prevent glutamate receptors from becoming overactivated. Moreover, glutamate in the blood is prevented from reaching the brain through the blood-brain barrier (1).
Clinical evidence suggests that Prozac has a broader binding profile, including 5HTRs and ion channels. The existence of several Prozac binding sites indicates that the drug may exert its antidepressant activity via different pathways.
One of the in vitro experimental data suggested that Prozac does not exert any effect on the EAAT3 (excitatory amino acid transporters) activity, but rather exerts its antidepressant effect by affecting GABAergic transmission nonspecifically. Eaat3, present in the plasma membrane of neurons and glial cells, helps in the extracellular uptake of glutamate and prevents glutamate-induced neuronal damage (2). However, modern research and experimental data suggest otherwise.
In chronic stress, the level of glutamate increases which ultimately leads to the atrophy of apical dendrites. Although the primary mechanism of action of Prozac is based on serotonergic system modulation, the final pathway appears to be the glutamatergic system (3).
Prozac inhibits glutamatergic and gamma-aminobutyric acid (GABA)-ergic synaptic release by reducing the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex function. On the flip side, it increases the extracellular serotonin level by the inhibition of SERT (serotonin transport) (3).
In another in vivo analysis, the authors established that Prozac therapy lowered the total quantity of glutamate and GABA transporters at individual synapses in primary cortical neurons (4).
What is the role of Prozac in ‘excitotoxicity’?
Glutamate exerts excitatory effects on nerve cells and can drive cells to death, a process known as ‘excitotoxicity’. It can occur due to excessive glutamate exposure or overstimulation of its membrane receptors, which results in neuronal harm or death (5).
Prozac alters the expression of glutamatergic receptor subunits. It inhibits the NMDA (N-methyl-D-aspartate) receptors, a glutamate receptor and ion channel found in the neurons, and may provide neuroprotection by modulating glutamatergic involvement in excitotoxicity (6).
Prozac has been reported to prevent excitotoxicity-induced oxidative stress and mitochondrial membrane potential impairment by preventing NO (nitric acid) and ROS (reactive oxygen species) production in mice (7).
Which medicines to avoid with Prozac?
Glutamate is essential for maintaining optimal energy levels, which are required for most CNC processes such as learning and memory, as well as neuroplasticity, which is required for adaptability to environmental changes (8). When it exceeds a certain concentration it can lead to toxicity and brain cell death.
Always take your medication of Prozac on time to avoid such circumstances. Also, avoid the use of monosodium glutamate (MSG, sodium salt of glutamic acid) under normal or stress conditions, especially if taking Prozac.
Do not combine Prozac with certain medications including MAOI (monoamine oxidase inhibitor), certain antipsychotics, tricyclic antidepressants, and Vyvanse. It can result in a serious condition of serotonin syndrome.
Conclusion
Call your doctor if you feel a sudden feeling of excitement, enthusiasm, restlessness or a state of euphoria. Bleeding gums, bruises and blood in cough are also reported serious side effects of the drug. Always consult your doctor before taking antidepressants and follow the dosage regimen strictly.
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References
1.-
Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. Journal of neural transmission. 2014 Aug;121:799-817. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133642/
2.-
Park HJ, Baik HJ, Kim DY, Lee GY, Woo JH, Zuo Z, Chung RK. Doxepin and imipramine but not fluoxetine reduce the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes. BMC anesthesiology. 2015 Dec;15(1):1-7.https://bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-015-0098-5
3.-
Lazarevic V, Mantas I, Flais I, Svenningsson P. Fluoxetine suppresses glutamate-and GABA-mediated neurotransmission by altering SNARE complex. International Journal of Molecular Sciences. 2019 Aug 30;20(17):4247.https://pubmed.ncbi.nlm.nih.gov/31480244/
4.-
Lazarevic V, Mantas I, Flais I, Svenningsson P. Fluoxetine suppresses glutamate-and GABA-mediated neurotransmission by altering SNARE complex. International Journal of Molecular Sciences. 2019 Aug 30;20(17):4247.https://www.mdpi.com/1422-0067/20/17/4247/htm
5.-
Mattson MP. Excitotoxicity. Neurodegeneration. 2017 Mar 29:37-45.https://www.sciencedirect.com/science/article/abs/pii/B9780128131466000114
6.-
Beshara S, Beston BR, Pinto JG, Murphy KM. Effects of fluoxetine and visual experience on glutamatergic and GABAergic synaptic proteins in adult rat visual cortex. Eneuro. 2015 Nov 1;2(6).https://www.eneuro.org/content/eneuro/2/6/ENEURO.0126-15.2015.full.pdf
7.-
Ludka FK, Dal-Cim T, Binder LB, Constantino LC, Massari C, Tasca CI. Atorvastatin and fluoxetine prevent oxidative stress and mitochondrial dysfunction evoked by glutamate toxicity in hippocampal slices. Molecular Neurobiology. 2017 Jul;54:3149-61.https://link.springer.com/article/10.1007/s12035-016-9882-6
8.-
Pal MM. Glutamate: The master neurotransmitter and its implications in chronic stress and mood disorders. Frontiers in human neuroscience. 2021 Oct 29;15:722323.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586693/
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