Physostigmine

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Structural formula
Structural formula of physostigmine
General
Surname Physostigmine
other names
  • (3a R , 8a S ) -1,3a, 8-trimethyl-1 H , 2 H , 3 H , 3 H , 8 H , 8a H -pyrrolo [2,3- b ] indol-5-yl N methylcarbamate
  • Eserin
Molecular formula C 15 H 21 N 3 O 2
External identifiers / databases
CAS number 57-47-6
EC number 200-332-8
ECHA InfoCard 100,000,302
PubChem 5983
DrugBank DB00981
Wikidata Q410595
Drug information
ATC code
Drug class

Parasympathomimetic

Mechanism of action

Cholinesterase inhibition

properties
Molar mass 275.35 g · mol -1
Physical state

firmly

Melting point

102-104 ° C

pK s value

6.12; 12.24

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary
06 - Toxic or very toxic

danger

H and P phrases H: 300-330
P: 260-284-301 + 310-320-405-501
Toxicological data

4.5 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Physostigmine is an indole alkaloid . It is used in medicine for certain postoperative disorders and as an antidote for poisoning with parasympatholytic substances that cause an anticholinergic syndrome .

Occurrence

Manchinelbaum ( Hippomane mancinella )

The seeds of the calabar bean ( Physostigma venenosum ) and the fruits of the Manchinel tree ( Hippomane mancinella ) contain physostigmine.

Clinical information

Physostigmine is an indirect parasympathomimetic (cholinergic), i.e. that is, it enhances the functioning of the parasympathetic nervous system in the body. As an acetylcholinesterase inhibitor, physostigmine delays the breakdown of acetylcholine and has an indirect parasympathomimetic effect by increasing the acetylcholine concentration at the receptor.

In the heart it leads to a decrease in frequency, in the eyes to a miosis (constriction of the pupil), in the bronchi to a constriction and in the intestine to a stimulation of the peristalsis .

It also unfolds its effect on the motorized end plate . Physostigmine is a tertiary amine and, in contrast to the quaternary amines such as e.g. B. neostigmine cross the blood-brain barrier and develop its effect in the CNS. For this reason, it is used to treat central anticholinergic syndrome (ZAS) , a post-operative disorder that can be caused by a number of anesthetics and drugs used in anesthesia.

Furthermore, the influence of physostigmine on certain phases in a septic process was investigated. It was shown that the immune system and the central nervous system (CNS) can influence each other.

The efferent part of an inflammatory reflex arc, described as the “cholinergic antiinflammatory pathway (CAP)”, is a mechanism of neuronal inflammation control. Cholinesterase inhibitors can inhibit the release of pro-inflammatory cytokines in the macrophages by activating the “cholinergic antiinflammatory pathway” via the autonomic nervous system . Cells of the immune system are reached via the efferent part of the vagus nerve , the neurotransmitter acetylcholine and the α7 subunit of the nicotinic acetylcholine receptor . So-called proinflammatory cytokines induce an increased release of corticotropin-releasing hormone (CRH) or arginine-vasopressin (AVP) in the hypothalamus and of adrenocorticotropic hormone (ACTH) in the pituitary gland . The resulting increased cortisol release unfolds its anti-inflammatory effect by suppressing NF-κB activation and by activating anti-inflammatory cytokines. In the celiac plexus, the information is probably passed on to postsynaptic sympathetic nerve fibers that run to the spleen and there act on cells of the immune system. Cholinesterase inhibitors, such as physostigmine, lead to anti-inflammatory effects in experimental sepsis if they are administered early.

Pharmacological properties

application

Physostigmine is used as an antidote for poisoning or overdosing

and used to treat central anticholinergic syndromes . Physostigmine is also used in ophthalmology as a miotic for constricting the pupils after administration of atropine for pupil dilation, for drug therapy of glaucoma and for lowering intraocular pressure . Other acetylcholinesterase inhibitors such as e.g. B. donepezil , rivastigmine or galantamine are used to treat dementia .

Physostigmine and the similar carbamate pyridostigmine are used for prophylaxis against poisoning with chemical warfare agents based on cholinesterase inhibitors .

Side effects

The following side effects can occur:

Contraindications

Physostigmine must not be used in the following diseases:

The simultaneous administration of other cholinesterase inhibitors must be avoided because of a mutual increase in effectiveness.

literature

  • Ernst Mutschler: drug effects: textbook of pharmacology and toxicology . 7., completely reworked. and exp. Edition. Knowledge Verl.-Ges, Stuttgart 1996, ISBN 3-8047-1377-7 .
  • Rolf Kretschmer: Emergency medication from A - Z: Clinic and pharmacology at a glance . 5th updated edition. Knowledge Verl.-Ges., Stuttgart 2005, ISBN 3-8047-2133-8 .

Trade names

Monopreparations

Anticholium (D, A)

former combination preparations

Eucard (D)

Web links

  • Entry on physostigmine at Vetpharm, accessed on August 11, 2012.

Individual evidence

  1. ↑ a b Datasheet Eserine at Sigma-Aldrich , accessed on April 20, 2011 ( PDF ).
  2. ^ Louis F. Fieser and Mary Fieser: Organic Chemistry , 2nd Edition, Verlag Chemie 1982, ISBN 3-527-25075-1 .
  3. ↑ a b Entry on Eserin in the GESTIS substance database of the IFA , accessed on July 23, 2016(JavaScript required) .
  4. ↑ Entry on Physostigmine in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
  5. ↑ Peter M. Lauven, H. Stoeckel: The central anticholinergic syndrome: Clinic and therapy. Current Neuropädiatrie 1986, pp. 177-185, doi : 10.1007 / 978-3-642-47569-6_19 .
  6. ↑ cholinergic anti-inflammatory control pathway
  7. ↑ Katja Weismüller, Michael Bauer, Stefan Hofer, Markus A. Weigand: The importance of the neuroendocrine axis in the pathophysiology of sepsis. Anästhesiol Intensivmed Emergency Med Schmerzther, Georg Thieme Verlag Stuttgart (2010); 45 (9): 574-579, doi : 10.1055 / s-0030-1265750 .
  8. ↑ Saskia Eckert: Development of a dynamic model for studying the protective effects of reversible acetylcholinesterase inhibitors against irreversible inhibition by highly toxic organophosphates . Munich 2006, DNB  982657064 , p. 1 , urn : nbn: de: bvb: 19-61966 (dissertation).
  9. ↑ Szinicz, L. and Baskin, SI: Chemical and biological warfare agents . In: Textbook of Toxicology . WV mbH. Stuttgart: 865-895, 1999.
  10. ↑ Eucard. (Advertisement by Südmedica GmbH, Munich) In: Munich Medical Weekly. Born 1953, No. 1 (January) 1953, p. CXXXV.