Cholinesterase inhibitor

Cholinesterase inhibitors, also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the synaptic cleft that can bind to muscarinic receptors, nicotinic receptors and others. This group of inhibitors are divided into two subgroups, acetylcholinesterase inhibitors and butyrylcholinesterase inhibitors.[1][2]

Not to be confused with anti-cholinergic or Cholinergic.

They may be used as drugs for Alzheimer's and myasthenia gravis, and also as chemical weapons and insecticides. Side effects when used as drugs may include loss of appetite, nausea, vomiting, loose stools, vivid dreams at night, dehydration, rash, bradycardia, peptic ulcer disease, seizures, weight loss, rhinorrhea, salivation, muscle cramps, fasciculations.[3][4]

Cholinesterase inhibitors are indirect-acting parasympathomimetic drug.[5]

Medical use
Further information: Donepezil § Medical uses

While 4 cholinesterase inhibitors are approved in the United States only three are available commercially.[3] The three available are rivastigmine, donepezil, and galantamine while tacrine is not.[3]

They are generally used to treat Alzheimer's disease and dementia.[3] If a benefit occurs this is generally at two to third month after starting.[3]

It's difficult to determine which cholinesterase inhibitor has greater efficacy due to design flaws in head-to-head comparison study.[6]

Cholinesterase inhibitor toxicity
Further information: Organophosphate poisoning and cholinergic crisis

Common Side effects include insomnia, nausea and vomiting, accidental injury, headache, dizziness, bradycardia, hypotension, ecchymosis, sleep disturbance[7]

Binding affinity

Acetylcholinesterase inhibitors

Donepezil, phenserine, huperzine A, and BW284c51 are selective AChE inhibitors. [8][6]

Butyrylcholinesterase inhibitor

Tetra (monoisopropyl) pyrophosphoramide (Iso-OMPA) and ethopropazine are selective BChE inhibitors.[8]

AChE & BChE inhibitor

Paraoxon and rivastigmine are both acetylcholinesterase inhibitor and butyrylcholinesterase inhibitor.[8][6][4]

USFDA's Administration Adverse Event Reporting System database compared rivastigmine to the other cholinesterase inhibiting drugs donepezil and galantamine found that rivastigmine was associated with a higher frequency of reports of death as an adverse event.[9]

Acetylcholinesterase inhibitors & nicotinic receptor modulator

Galantamine might be less well tolerated than donepezil and rivastigmine.[6]

History

Given the cognitive-enhancing property of nicotine and higher-than-expected overlap in cigarette smoking in people with ADHD regardless of age, researchers believe there exists a link between nicotine and ADHD.[10] Afterwards, the transdermal nicotine has proved reducing ADHD symptoms in adolescents and adults, which in turn contributed to their cessation of smoking.[10] ABT-418 and ABT-089 (Pozanicline) are the leading candidate agents.[10]

gollark: Added to your apiological profile. However, beware (apioforms) as I CAN choose new ones at any time.
gollark: Please don't use this if you need sub-minute accuracy.
gollark: Joe's homework and its lateness.
gollark: https://osmarks.tk/radio/
gollark: No randomly generated humor.

See also

Further reading
  • Institute, National; (UK), Care Excellence (2019-12-27). "Cholinesterase inhibitors and memantine for dementia". NCBI Bookshelf. Retrieved 2019-12-27.
  • Parsons, Chris G.; Danysz, Wojciech; Dekundy, Andrzej; Pulte, Irena (2013-05-09). "Memantine and Cholinesterase Inhibitors: Complementary Mechanisms in the Treatment of Alzheimer's Disease". Neurotoxicity Research. Springer Science and Business Media LLC. 24 (3): 358–369. doi:10.1007/s12640-013-9398-z. ISSN 1029-8428. PMC 3753463. PMID 23657927.
  • Meng, Yan‑Hong; Wang, Pan‑Pan; Song, Ya‑Xue; Wang, Jian‑Hua (2019-03-01). "Cholinesterase inhibitors and memantine for Parkinson's disease dementia and Lewy body dementia: A meta‑analysis". Experimental and Therapeutic Medicine. 17 (3): 1611–1624. doi:10.3892/etm.2018.7129. ISSN 1792-0981. Retrieved 2019-12-27.

References
  1. English, Brett A.; Webster, Andrew A. (2012). "Acetylcholinesterase and its Inhibitors". Primer on the Autonomic Nervous System. Elsevier. pp. 631–633. doi:10.1016/b978-0-12-386525-0.00132-3. ISBN 978-0-12-386525-0.
  2. Deutch, Ariel Y.; Roth, Robert H. (2014). "Pharmacology and Biochemistry of Synaptic Transmission". From Molecules to Networks. Elsevier. pp. 207–237. doi:10.1016/b978-0-12-397179-1.00007-5. ISBN 978-0-12-397179-1.
  3. Budson, Andrew E.; Solomon, Paul R. (2016). "Cholinesterase Inhibitors". Memory Loss, Alzheimer's Disease, and Dementia. Elsevier. pp. 160–173. doi:10.1016/b978-0-323-28661-9.00016-0. ISBN 978-0-323-28661-9.
  4. Khoury, Rita; Rajamanickam, Jayashree; Grossberg, George T. (2018-01-08). "An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine". Therapeutic Advances in Drug Safety. SAGE Publications. 9 (3): 171–178. doi:10.1177/2042098617750555. ISSN 2042-0986. PMC 5810854. PMID 29492246.
  5. Forrester, John V.; Dick, Andrew D.; McMenamin, Paul G.; Roberts, Fiona; Pearlman, Eric (2016). "General and ocular pharmacology". The Eye. Elsevier. pp. 338–369.e1. doi:10.1016/b978-0-7020-5554-6.00006-x. ISBN 978-0-7020-5554-6. Parasympathomimetics are a group of drugs that act either by directly stimulating the muscarinic receptor, for example pilocarpine, or by inhibiting the enzyme acetylcholinesterase, which hydrolyses the acetylcholine in the synapse.
  6. Hersen, Michel (2006). Comprehensive handbook of personality and psychopathology (Tertiary source). Hoboken, N.J: John Wiley. p. 514. ISBN 978-0-471-75725-2. OCLC 63041762.
  7. Pfizer. "prescribing information" (PDF). FDA access data. Pfizer. Retrieved 2012. Check date values in: |accessdate= (help)
  8. Waiskopf, Nir; Soreq, Hermona (2015). "Cholinesterase Inhibitors". Handbook of Toxicology of Chemical Warfare Agents. Elsevier. pp. 761–778. doi:10.1016/b978-0-12-800159-2.00052-x. ISBN 978-0-12-800159-2.
  9. Ali TB, Schleret TR, Reilly BM, Chen WY, Abagyan R (2015). "Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada". PLOS ONE. 10 (12): e0144337. Bibcode:2015PLoSO..1044337A. doi:10.1371/journal.pone.0144337. PMC 4671709. PMID 26642212.
  10. Brown, Thomas (2009). ADHD comorbidities : handbook for ADHD complications in children and adults (Tertiary source). Washington, DC: American Psychiatric Pub. p. 353. ISBN 978-1-58562-158-3. OCLC 244601824.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.