The nemertine toxin anabaseine and its derivative DMXBA (GTS-21): Chemical and pharmacological properties

William Kem, Ferenc Soti, Kristin Wildeboer, Susan LeFrancois, Kelly MacDougall, Dong Qing Wei, Kuo Chen Chou, Hugo R. Arias

Research output: Contribution to journalReview article

45 Citations (Scopus)

Abstract

Nemertines are a phylum of carnivorous marine worms that possess a variety of alkaloidal, peptidic or proteinaceous toxins that serve as chemical defenses against potential predators. The hoplonemertines additionally envenomate their prey with a mixture of proboscis alkaloids delivered with the help of a calcareous stylet that punctures the skin of the victim. Anabaseine, the first of these alkaloids to be identified, stimulates a wide variety of animal nicotinic acetylcholine receptors (AChRs), especially the neuromuscular [e.g., α1 2β1γδ (embryogenic) or α1 2β1γε (adult)] and α7 AChRs that are inhibited by the snake peptide α-bungarotoxin. A synthetic derivative, 3-(2,4-Dimethoxybenzylidene)-Anabaseine (DMXBA; also called GTS-21), improves memory in experimental animals and humans and is currently in clinical trials to determine whether it can ameliorate cognitive problems associated with schizophrenia. Here we summarize present knowledge concerning the chemistry and mechanisms of action of these two substances (anabaseine and DMXBA) on AChRs, especially those found in the mammalian brain.

Original languageEnglish
Pages (from-to)255-273
Number of pages19
JournalMarine Drugs
Volume4
Issue number3
DOIs
StatePublished - 1 Apr 2006
Externally publishedYes

Fingerprint

Pharmacology
Cholinergic Receptors
Alkaloids
Bungarotoxins
Snakes
Nicotinic Receptors
Punctures
Schizophrenia
Clinical Trials
Skin
Peptides
3-(2,4-dimethoxybenzylidene)anabaseine
anabaseine
Brain

Keywords

  • Anabaseine
  • Cognition
  • DMXBA
  • GTS-21
  • Nemertine
  • Nicotinic receptors

Cite this

Kem, William ; Soti, Ferenc ; Wildeboer, Kristin ; LeFrancois, Susan ; MacDougall, Kelly ; Wei, Dong Qing ; Chou, Kuo Chen ; Arias, Hugo R. / The nemertine toxin anabaseine and its derivative DMXBA (GTS-21) : Chemical and pharmacological properties. In: Marine Drugs. 2006 ; Vol. 4, No. 3. pp. 255-273.
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Kem, W, Soti, F, Wildeboer, K, LeFrancois, S, MacDougall, K, Wei, DQ, Chou, KC & Arias, HR 2006, 'The nemertine toxin anabaseine and its derivative DMXBA (GTS-21): Chemical and pharmacological properties', Marine Drugs, vol. 4, no. 3, pp. 255-273. https://doi.org/10.3390/md403255

The nemertine toxin anabaseine and its derivative DMXBA (GTS-21) : Chemical and pharmacological properties. / Kem, William; Soti, Ferenc; Wildeboer, Kristin; LeFrancois, Susan; MacDougall, Kelly; Wei, Dong Qing; Chou, Kuo Chen; Arias, Hugo R.

In: Marine Drugs, Vol. 4, No. 3, 01.04.2006, p. 255-273.

Research output: Contribution to journalReview article

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T1 - The nemertine toxin anabaseine and its derivative DMXBA (GTS-21)

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AU - Kem, William

AU - Soti, Ferenc

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AU - LeFrancois, Susan

AU - MacDougall, Kelly

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AU - Chou, Kuo Chen

AU - Arias, Hugo R.

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AB - Nemertines are a phylum of carnivorous marine worms that possess a variety of alkaloidal, peptidic or proteinaceous toxins that serve as chemical defenses against potential predators. The hoplonemertines additionally envenomate their prey with a mixture of proboscis alkaloids delivered with the help of a calcareous stylet that punctures the skin of the victim. Anabaseine, the first of these alkaloids to be identified, stimulates a wide variety of animal nicotinic acetylcholine receptors (AChRs), especially the neuromuscular [e.g., α1 2β1γδ (embryogenic) or α1 2β1γε (adult)] and α7 AChRs that are inhibited by the snake peptide α-bungarotoxin. A synthetic derivative, 3-(2,4-Dimethoxybenzylidene)-Anabaseine (DMXBA; also called GTS-21), improves memory in experimental animals and humans and is currently in clinical trials to determine whether it can ameliorate cognitive problems associated with schizophrenia. Here we summarize present knowledge concerning the chemistry and mechanisms of action of these two substances (anabaseine and DMXBA) on AChRs, especially those found in the mammalian brain.

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