Cotinine, a neuroactive metabolite of nicotine: Potential for treating disorders of impaired cognition

Alvin V Terry, Caterina M. Hernandez, Elizabeth J. Hohnadel, Kristy P. Bouchard, Jerry J. Buccafusco

Research output: Contribution to journalReview article

53 Citations (Scopus)

Abstract

The pharmacological effects of the tobacco-derived alkaloid nicotine have been widely studied in humans and animals for decades. However, relatively little attention has been given to the potential actions of its major metabolite, cotinine. After nicotine consumption the duration of cotinine's presence in blood and brain greatly exceeds that of nicotine. Therefore, cotinine could mediate the more protracted pharmacological effects of nicotine. The studies described in this report were thus designed to further investigate certain neuropharmacological actions of cotinine. Behavioral tests (e.g., delayed matching-to-sample) were conducted in aged rhesus monkeys to assess the effects of cotinine on working memory and attention. In rats a prepulse inhibition (PPI) procedure was used to assess the effects of the compound on auditory gating - a method for predicting the potential antipsychotic properties of drugs. Cotinine exhibited significant effectiveness in these tasks. The drug was also cytoprotective in differentiated PC-12 cells with a potency equivalent to that of nicotine. The effects of chronic cotinine treatment on the expression of nicotinic and muscarinic acetylcholine receptors in rat brain were measured by [125I]epibatidine, [125I]α-bungarotoxin ([125I]BTX), [3H]pirenzepine ([3H]PRZ), and [3H]AFDX-384 ([3H]AFX) autoradiography. Unlike nicotine, cotinine failed to upregulate the expression of brain nicotinic receptors. Based on its relative safety in man, cotinine should prove useful in the treatment of diseases of impaired cognition and behavior without exhibiting the toxicity usually attributed to nicotine.

Original languageEnglish (US)
Pages (from-to)229-252
Number of pages24
JournalCNS Drug Reviews
Volume11
Issue number3
StatePublished - Sep 1 2005

Fingerprint

Cognition Disorders
Cotinine
Nicotine
epibatidine
Nicotinic Receptors
Brain
Pharmacology
Pirenzepine
Bungarotoxins
Muscarinic Receptors
Macaca mulatta
Autoradiography
Short-Term Memory
Alkaloids
Cognition
Antipsychotic Agents
Action Potentials
Tobacco
Up-Regulation

Keywords

  • Attention
  • Cognition
  • Cotinine
  • Cytoprotection
  • Delayed response task
  • Memory
  • Nicotine
  • Nicotinic receptors
  • Non-human primates
  • Prepulse inhibition

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Pharmacology

Cite this

Terry, A. V., Hernandez, C. M., Hohnadel, E. J., Bouchard, K. P., & Buccafusco, J. J. (2005). Cotinine, a neuroactive metabolite of nicotine: Potential for treating disorders of impaired cognition. CNS Drug Reviews, 11(3), 229-252.

Cotinine, a neuroactive metabolite of nicotine : Potential for treating disorders of impaired cognition. / Terry, Alvin V; Hernandez, Caterina M.; Hohnadel, Elizabeth J.; Bouchard, Kristy P.; Buccafusco, Jerry J.

In: CNS Drug Reviews, Vol. 11, No. 3, 01.09.2005, p. 229-252.

Research output: Contribution to journalReview article

Terry, AV, Hernandez, CM, Hohnadel, EJ, Bouchard, KP & Buccafusco, JJ 2005, 'Cotinine, a neuroactive metabolite of nicotine: Potential for treating disorders of impaired cognition', CNS Drug Reviews, vol. 11, no. 3, pp. 229-252.
Terry AV, Hernandez CM, Hohnadel EJ, Bouchard KP, Buccafusco JJ. Cotinine, a neuroactive metabolite of nicotine: Potential for treating disorders of impaired cognition. CNS Drug Reviews. 2005 Sep 1;11(3):229-252.
Terry, Alvin V ; Hernandez, Caterina M. ; Hohnadel, Elizabeth J. ; Bouchard, Kristy P. ; Buccafusco, Jerry J. / Cotinine, a neuroactive metabolite of nicotine : Potential for treating disorders of impaired cognition. In: CNS Drug Reviews. 2005 ; Vol. 11, No. 3. pp. 229-252.
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