Biperiden

Last updated
Biperiden
Biperiden Stereoisomers.png
Biperiden-3D-sticks.png
Clinical data
Trade names Akineton
AHFS/Drugs.com Monograph
MedlinePlus a699058
License data
Pregnancy
category
  • AU:B2
Routes of
administration
By mouth, intramuscular injection (IM), intravenous therapy (IV)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 33 ± 5% (by mouth)
Protein binding 60%
Metabolism Liver hydroxylation
Elimination half-life 18 to 24 hours
Excretion Kidney
Identifiers
  • (1RS,2SR,4RS)-1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-phenyl-3-(piperidin- 1-yl)propan-1-ol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.441 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H29NO
Molar mass 311.469 g·mol−1
3D model (JSmol)
  • OC(c1ccccc1)(CCN2CCCCC2)C4C3\C=C/C(C3)C4
  • InChI=1S/C21H29NO/c23-21(19-7-3-1-4-8-19,11-14-22-12-5-2-6-13-22)20-16-17-9-10-18(20)15-17/h1,3-4,7-10,17-18,20,23H,2,5-6,11-16H2 Yes check.svgY
  • Key:YSXKPIUOCJLQIE-UHFFFAOYSA-N Yes check.svgY
   (verify)

Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease, certain drug-induced movement disorders [2] and Tourette Syndrome [ citation needed ]. It is not recommended for tardive dyskinesias. [3] It is taken by mouth, injection into a vein, or muscle. [2] [3]

Contents

Common side effects include blurred vision, dry mouth, sleepiness, constipation, and confusion. [2] It should not be used in people with a bowel obstruction or glaucoma. [2] It is unclear if use in pregnancy or breastfeeding is safe. [4] Biperiden is in the anticholinergic family of medication. [2]

Biperiden was approved for medical use in the United States in 1959. [2] It is on the World Health Organization's List of Essential Medicines. [5] Biperiden is no longer marketed in the United States. [6] [7] [8]

Medical uses

Biperiden is used for the adjunctive treatment of all forms of Parkinson's disease (postencephalitic, idiopathic, and arteriosclerotic Parkinson's) and for reduced sweating in methadone users. It seems to exert better effects in the postencephalitic and idiopathic than in the arteriosclerotic type.

Biperiden is also commonly used to improve acute extrapyramidal side effects related to antipsychotic drug therapy, such as akathisia.

It relieves muscle rigidity, reduces abnormal sweating related with clozapine and methadone use [9] [10] and salivation, improves abnormal gait, and to lesser extent, tremor.

In its role as a synthetic acetylcholine antagonist, biperiden has been analyzed as an alternative anticonvulsant for usage in the treatment of intoxication by organophosphorus nerve agents, such as sarin. [11]

It was also suggested by IV route for neuroleptic malignant syndrome. [12]

Pregnancy and lactation

Children

Children and adolescents aged 1 year and older may be treated. The clinical experience is mainly on the short-term treatment of acute drug induced dystonic reactions. Doses should be reduced according to the weight of the patients.[ citation needed ]

Contraindications

Side effects

Dose-dependent side effects are frequent. Particularly geriatric patients may react with confusional states or develop delirium.

Interactions

Overdose

Biperiden mimics an atropine intoxication with mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particular in children. Premortal signs are respiratory depression and cardiac arrest. A specific antagonist is physostigmine which combines a peripheral and a central action. Carbachol can be used to treat atonic bowels and bladder. The vital functions should be monitored and stabilized. It may be necessary to treat hyperthermia with cooling blankets.

Pharmacokinetics

The oral bioavailability is only 33 ± 5% due to extensive first-pass metabolism. In young, healthy volunteers, peak plasma concentrations following a single oral 4 mg immediate-release dose are reached after 1.5 hours. The elimination half-life has been determined as 18.4 hours, and may be prolonged in geriatric patients. After a 4 mg intravenous dose, the elimination half-life is approximately 24 hours.

Pharmacology

Biperiden has an atropine-like blocking effect on all peripheral structures which are parasympathetic-innervated (e.g. cardiovascular and visceral organs). It also has a prominent central blocking effect on M1 receptors. Biperiden does also act as FIASMA (functional inhibitor of acid sphingomyelinase). [14]

History

Biperiden was synthesized by the German chemist W. Klavehn from Knoll AG, Germany. In March 1953 a patent was applied for in Germany [15] and subsequently in many other countries. A US patent application was filed in March 1954 and granted in April 1957. [16]

One website reported that it was not commercially available in the United States as of 2017. [17]

Related Research Articles

3-Quinuclidinyl benzilate (QNB) is an odorless and bitter-tasting military incapacitating agent. BZ is an antagonist of muscarinic acetylcholine receptors whose structure is the ester of benzilic acid with an alcohol derived from quinuclidine.

<span class="mw-page-title-main">Atropine</span> Anticholinergic medication used as antidote for nerve agent poisoning

Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle. Eye drops are also available which are used to treat uveitis and early amblyopia. The intravenous solution usually begins working within a minute and lasts half an hour to an hour. Large doses may be required to treat some poisonings.

<span class="mw-page-title-main">Benzatropine</span> Medication for movement disorders

Benzatropine (INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is not useful for tardive dyskinesia. It is taken by mouth or by injection into a vein or muscle. Benefits are seen within two hours and last for up to ten hours.

<span class="mw-page-title-main">Cyclopentolate</span> Pair of enantiomers

Cyclopentolate is a muscarinic antagonist. It is commonly used as an eye drop during pediatric eye examinations to dilate the eye (mydriatic) and prevent the eye from focusing/accommodating (cycloplegic). Cyclopentolate or atropine can also be administered to reverse muscarinic and central nervous system effects of indirect cholinomimetic (anti-AChase) administration.

Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.

<span class="mw-page-title-main">Pilocarpine</span> Medication used to treat glaucoma and dry mouth

Pilocarpine is a medication used to reduce pressure inside the eye and treat dry mouth. As an eye drop it is used to manage angle closure glaucoma until surgery can be performed, ocular hypertension, primary open angle glaucoma, and to constrict the pupil after dilation. However, due to its side effects it is no longer typically used for long-term management. Onset of effects with the drops is typically within an hour and lasts for up to a day. By mouth it is used for dry mouth as a result of Sjögren syndrome or radiation therapy.

<span class="mw-page-title-main">Physostigmine</span> Chemical compound

Physostigmine is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Amantadine</span> Medication used to treat dyskinesia

Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because of widespread drug resistance. It acts as a nicotinic antagonist, dopamine agonist, and noncompetitive NMDA antagonist. The antiviral mechanism of action is antagonism of the influenzavirus A M2 proton channel, which prevents endosomal escape.

Diphenoxylate/atropine, also known as co-phenotrope, is a combination of the medications diphenoxylate and atropine, used to treat diarrhea. It should not be used in those in whom Clostridioides difficile infection is a concern. It is taken by mouth. Onset is typically within an hour.

<span class="mw-page-title-main">Diphenoxylate</span> Centrally active opioid drug used for the treatment of diarrhea

Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine is present to prevent drug abuse and overdose. It should not be given to children due to the risk that they will stop breathing and should not be used in people with Clostridium difficile infection.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Chlorprothixene</span> Typical antipsychotic medication

Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.

<span class="mw-page-title-main">Cyclizine</span> Medication for motion sickness or vertigo

Cyclizine, sold under a number of brand names, is a medication used to treat and prevent nausea, vomiting and dizziness due to motion sickness or vertigo. It may also be used for nausea after general anaesthesia or that which developed from opioid use. It is taken by mouth, in the rectum, or injected into a vein.

<span class="mw-page-title-main">Trihexyphenidyl</span> Antispasmodic drug

Trihexyphenidyl is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of Parkinson's disease. It was approved by the FDA for the treatment of Parkinson's in the US in 2003.

<span class="mw-page-title-main">Oxybutynin</span> Medication for overactive bladder

Oxybutynin, sold as under the brand name Ditropan among others, is an anticholinergic drug primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect profile, broad applicability, and continued efficacy over long periods of time. It works similar to tolterodine, darifenacin, and solifenacin, although it is usually preferred over these medications. It is sometimes used off-label for treatment of hyperhidrosis, or excessive sweating. It has also been used off-label to treat bed wetting in children, but this use has declined, as it is most likely ineffective in this role. It is taken by mouth or applied to the skin.

<span class="mw-page-title-main">Tropicamide</span> Chemical compound

Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effects occur within 40 minutes and last for up to a day.

<span class="mw-page-title-main">Procyclidine</span> Group of stereoisomers

Procyclidine is an anticholinergic drug principally used for the treatment of drug-induced parkinsonism, akathisia and acute dystonia, Parkinson's disease, and idiopathic or secondary dystonia.

<span class="mw-page-title-main">Bornaprine</span> Chemical compound

Bornaprine is a synthetic anticholinergic medication that is primarily used to treat Parkinson's disease. Additionally, bornaprine has been used to treat other disorders, including hyperhidrosis.

Flupentixol/melitracen is a combination of two psychoactive agents flupentixol and melitracen. It is designed for short term usage only. It is produced by Lundbeck.

References

  1. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. 1 2 3 4 5 6 "Biperiden Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  3. 1 2 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 243. hdl: 10665/44053 . ISBN   9789241547659.
  4. "Biperiden Use During Pregnancy | Drugs.com". www.drugs.com. Archived from the original on 21 December 2016. Retrieved 15 December 2016.
  5. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. "Akineton (biperiden hydrochloride): FDA-Approved Drugs". U.S. Food and Drug Administration. Retrieved 2 July 2020.
  7. "Akineton (biperiden lactate): FDA-Approved Drugs". U.S. Food and Drug Administration. Retrieved 2 July 2020.
  8. "Akineton Tablets (biperiden hydrochloride)". DailyMed. Retrieved 2 July 2020.
  9. Richardson C, Kelly DL, Conley RR (August 2001). "Biperiden for excessive sweating from clozapine". Am J Psychiatry. 158 (8): 1329–30. doi:10.1176/appi.ajp.158.8.1329-a. PMID   11481174. Archived from the original on 2012-09-21. Retrieved 2008-11-12.
  10. Caflisch C, Figner B, Eich D (February 2003). "Biperiden for excessive sweating from methadone". Am J Psychiatry. 160 (2): 386–7. doi:10.1176/appi.ajp.160.2.386. PMID   12562595.
  11. Shih TM, McDonough JH (May 2000). "Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication". Archives of Toxicology. 74 (3): 165–172. doi:10.1007/s002040050670. PMID   10877003. S2CID   13749842. Archived from the original on September 23, 2017.
  12. Margetić B, Aukst-Margetić B (May 2010). "Neuroleptic malignant syndrome and its controversies". Pharmacoepidemiology and Drug Safety. 19 (5): 429–435. doi:10.1002/pds.1937. PMID   20306454. S2CID   2457321.
  13. Nishiyama K, Mizuno T, Sakuta M, Kurisaki H (1993). "Chronic dementia in Parkinson's disease treated by anticholinergic agents. Neuropsychological and neuroradiological examination". Adv Neurol. 60: 479–83. PMID   8420174.
  14. Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8): e23852. Bibcode:2011PLoSO...623852K. doi: 10.1371/journal.pone.0023852 . PMC   3166082 . PMID   21909365.
  15. DE 1005067,Klavehn W,"Verfahren zur Herstellung von bicyclisch substituierten Aminopropanolen",issued 1957, assigned to Knoll AG.
  16. US 2789110,Klavehn W,"Amino alcohols substituted by bicycloalkyl residues and a process of making same",issued 1957, assigned to Knoll AG.
  17. "Biperiden". Davis's Drug Guide. Archived from the original on 10 September 2017. Retrieved 6 July 2017.