Physostigmine: A Plant Alkaloid Isolated from Physostigma venenosum: A Review on Pharmacokinetics, Pharmacological and Toxicological Activities
Abstract
Medicinal plants have been documented as an important source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Strikingly, previous reports stated that natural products and their derived compounds exhibit lesser side effects and improved efficacy than other synthetic counterparts. Physostigmine, a parasympathomimetic plant alkaloid isolated from the West African perennial shrub Physostigma venenosum, it shows a narrow therapeutic index and a short life span, despite its ability to penetrate the blood-brain barrier (BBB). It is a widely known reversible butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) inhibitor and has been documented to treat various ailments such as Alzheimer’s disease. Pharmacologically, physostigmine was first reported as an antidote for atropine scopolamine and belladonna alkaloids toxicity. Recently, it has been documented as a therapy for treating several ailments including glaucoma, myasthenia gravis and the intoxication caused by tricyclic antidepressant overdoses, anti-histamines, antipsychotics, and benzodiazepines. Physostigmine has been reported to be absorbed from the gastrointestinal tract and showed short half-life, as, after the oral administration of 2 mg of physostigmine salicylate, the peak plasma concentration reached to 30 minutes. This review examines the biological activities, pharmacokinetics, and toxicity of physostigmine extracted from P. venenosum.
Keywords: Physostigma venenosum, Physostigmine, pharmacological activities, acetylcholinesterase and butyrylcholinesterase inhibitor.
Keywords:
Physostigma venenosum, Physostigmine, acetylcholinesterase, butyrylcholinesterase inhibitorDOI
https://doi.org/10.22270/jddt.v10i1-s.3866References
Orhan G, Orhan I, Subutay-Oztekin N, et al, Contemporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease. Recent patents on CNS drug discovery, 2009; 4: 43-51.
Comunián-Carrasco G, Peña-Martí GE, Martí-Carvajal AJ, Antibiotics for treating gonorrhoea in pregnancy. The Cochrane database of systematic reviews, 2018; 2(2): CD011167.
Nickalls RW, Nickalls EA, The first use of physostigmine in the treatment of atropine poisoning. A translation of Kleinwachter's paper entitled 'Observations on the effect of Calabar bean extract as an antidote to atropine poisoning'. Anaesthesia. 1988; 43: 776-779.
Triggle DM, Mitchell J, Filler R, The pharmacology of physostigmine. CNS Drug Reviews, 2006; 4: 87-136.
Singh A, Srivastava PS, Asad M, et al, A review on physostigmine: as antidote and treatment on Alzheimer's disease. International Journal of Pharmaceutical and Analytical Research, 2015; 4: 512-517.
Kerr GW, McGuffie AC, Wilkie S, Tricyclic antidepressant overdose: a review. Emergency Medicine Journal, 2001; 18: 236-241.
Lee J-H, Turndorf H and Poppers PJ, Physostigmine reversal of antihistamine-induced excitement and depression. Anesthesiology, 1975; 43: 683-684.
Beilin B, Vatashsky E, Weinstock M, Physostigmine as an antidote for poisoning by combination of thioridazine and trihexyphenidyl. The British journal of clinical practice, 1985; 39: 400-401.
Lorke DE, Petroianu GA, Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A review. Journal of Applied Toxicology, 2019; 39(1): 101-116.
Somani SM, Pharmacokinetics and pharmacodynamics of physostigmine in the rat after oral administration. Biopharmaceutics & Drug Disposition, 1989; 10: 187-203.
Morales-Ríos MS, Bucio MA, Joseph-Nathan P, Formal synthesis of (±)-physostigmine. Tetrahedron. 1996; 52: 5339-5348.
Walter K, Muller M, Bark worth M, et al, Pharmacokinetics of physostigmine in man following a single application of a transdermal system. The British journal of clinical pharmacology, 1995; 39: 59-63.
Allen N, Burns A, The treatment of Alzheimer's disease. Journal of Psychopharmacology, 1995; 9: 43-56.
Gleason MN, Gosselin RE, Hodge H, et al, Clinical toxicology of commercial products–acute poisoning (home and farm) Paltimore, Md., Williams and Wilkins: 130. Journal of the American Pharmaceutical Association, 1957; 46: 748-748.
Firestone JA, Smith-Weller T, Franklin G, et al, Pesticides and risk of Parkinson disease: a population-based case-control study. Archives of neurology, 2005; 62: 91-95.
Watkins JW, Schwarz ES, Arroyo-Plasencia AM, Mullins ME, Toxicology investigators consortium investigators. The use of physostigmine by toxicologists in anticholinergic toxicity. Journal of Medical Toxicology, 2015; 11(2): 179-184.
Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM, Acetylcholinesterase inhibitors: pharmacology and toxicology. Current Neuropharmacology, 2013; 11(3): 315–335.
Andrade OA, Zafar Gondal A, Physostigmine. [Updated 2019 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545261.0
Peter JV, Sudarsan TI, Moran JL, Clinical features of organophosphate poisoning: A review of different classification systems and approaches. Indian Journal of Critical Care Medicine, 2014; 18(11): 735–745.
Folch J, Petrov D, Ettcheto M, Abad S, Sánchez-López E, García ML, Olloquequi J, Beas-Zarate C, Auladell C, Camins A, Current research therapeutic strategies for Alzheimer's disease treatment. Neural Plasticity, 2016; 2016: 8501693.
Giacobini E, Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacological Research, 2004; 50: 433-440.
Fang L, Kraus B, Lehmann J, et al, Design and synthesis of tacrine ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates. Bioorganic & Medicinal Chemistry Letters, 2008; 18: 2905-2909.
Maurer SV, Williams CL, The cholinergic system modulates memory and hippocampal plasticity via its interactions with non-neuronal cells. Frontiers in Immunology, 2017; 8: 1489.
Perry EK, Tomlinson BE, Blessed G, et al, Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. British medical journal, 1978; 2: 1457-1459.
Bartus RT, Dean RL, Tetrahydroaminoacridine, 3, 4 diaminopyridine and physostigmine: direct comparison of effects on memory in aged primates. Neurobiology of Aging, 1988; 9: 351-356.
Dhingra D, Kumar V, Memory-enhancing activity of palmatine in mice using elevated plus maze and Morris water maze. Advances in Pharmacological Sciences, 2012; 2012: 357368.
Batiha GE-S, Beshbishy AA, Tayebwa DS, Shaheen MH, Yokoyama N, Igarashi I, Inhibitory effects of Uncaria tomentosa bark, Myrtus communis roots, Origanum vulgare leaves and Cuminum cyminum seeds extracts against the growth of Babesia and Theileria in vitro. Japanese Journal of Veterinary Parasitology, 2018; 17: 1-13.
Batiha GE-S, Beshbishy AM, Tayebwa DS, Adeyemi OS, Shaheen H, Yokoyama N, et al, The effects of trans-chalcone and chalcone 4 hydrate on the growth of Babesia and Theileria. PLoS Neglected of Tropical Disease, 2019a; 13: e0007030.
Beshbishy AM, Batiha GE, Yokoyama N, Igarashi I, Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo. Parasits and Vectors, 2019a; 12: 269.
Batiha GE-S, Beshbishy AA, Tayebwa DS, Shaheen MH, Yokoyama N, Igarashi I, Inhibitory effects of Syzygium aromaticum and Camellia sinensis methanolic extracts on the growth of Babesia and Theileria parasites. Ticks and Tick-borne Disease, 2019b; 10: 949-958.
Schmitt B, Bernhardt T, Moeller H-J, et al, Combination therapy in Alzheimer’s disease. CNS Drugs, 2004; 18: 827-844.
Hager K, Marahrens A, Kenklies M, et al, Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Archives of Gerontology and Geriatrics, 2001; 32: 275-282.
Van Dyck CH, Newhouse P, Falk WE, et al, Extended-release physostigmine in Alzheimer disease: a multicenter, double-blind, 12-week study with dose enrichment. Archives Of General Psychiatry, 2000; 57: 157-164.
Sahoo AK, Dandapat J, Dash UC, Kanhar S, Features and outcomes of drugs for combination therapy as a multi-targets strategy to combat Alzheimer's disease. Journal of Ethnopharmacology, 2018; 215: 42-73.
Kaye S, Handbook of emergency toxicology: a guide for the identification, diagnosis and treatment of poisoning. 5th ed. Charles C Thomas Pub Ltd, 1970; 1988: 31-44.
Hartvig P, Lindström B, Pettersson E, et al, Reversal of postoperative somnolence using a two‐rate infusion of physostigmine. Acta Anaesthesiologica Scandinavica, 1989; 33: 681-685.
Arens AM, Kearney TJ, Med, Adverse Effects of Physostigmine. Toxicology, 2019; 15: 184.
Coelho F and Birks J, Physostigmine for Alzheimer's disease. Cochrane database of systematic reviews, 2001; (2): CD001499.
Published
Abstract Display: 4379 
PDF Downloads: 2227 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.