Evidence for positive allosteric modulation of cognitive-enhancing effects of nicotine in healthy human subjects.
Rationale: Cognitive benefits of nicotinic acetylcholine receptor (nAChR) agonists are well established but have generally been of small magnitude and uncertain clinical significance. A way of raising the effect size may be to facilitate agonist-induced responses by co-administering a nAChR positive...
| Publicado en: | Psychopharmacology Vol. 237; no. 1; pp. 219 - 231 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jan2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141132767&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141132767 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Jan2020 vid: 237 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 141132767 10.1007/s00213-019-05363-4 141132767 ppf: 219 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Evidence for positive allosteric modulation of cognitive-enhancing effects of nicotine in healthy human subjects. aug: au: Hahn, Britta Shrieves, Megan E. Olmstead, Cory K. Yuille, Marie B. Chiappelli, Joshua J. Pereira, Edna F. R. Albuquerque, Edson X. Fawcett, William P. affil: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, P.O. Box 21247, 21228, Baltimore, MD, USA sug: ab: Rationale: Cognitive benefits of nicotinic acetylcholine receptor (nAChR) agonists are well established but have generally been of small magnitude and uncertain clinical significance. A way of raising the effect size may be to facilitate agonist-induced responses by co-administering a nAChR positive allosteric modulator (PAM). Objective: The aim was to test whether galantamine, a PAM at several nAChR subtypes, can potentiate the cognitive-enhancing effects of nicotine. Methods: Twenty-six adult never-smokers were treated, in a double-blind counterbalanced sequence, with nicotine (7 mg/24 h, transdermally) and galantamine (4 mg, p.o.) combined, nicotine alone, galantamine alone, and double placebo. A low dose of galantamine was chosen to minimize acetylcholinesterase inhibition, which was verified in blood assays. In each condition, participants were tested with three cognitive tasks. Results: Nicotine significantly improved reaction time (RT) and signal detection in a visuospatial attention task and the Rapid Visual Information Processing Task. Galantamine did not modulate these effects. A trend toward RT reduction by galantamine correlated with acetylcholinesterase inhibition. In a change detection task, there were no effects of nicotine or galantamine alone on accuracy or RT. However, both drugs combined acted synergistically to reduce RT. This effect was not associated with acetylcholinesterase inhibition. Conclusions: A pattern consistent with allosteric potentiation of nicotine effects by galantamine was observed on one of six performance measures. This may reflect specific nAChR subtype involvement, or additional pharmacological actions of galantamine may have overshadowed similar interactions on other measures. The finding suggests that allosteric potentiation of nAChR agonist-induced cognitive benefits is possible in principle. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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