Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model

Molchan, Susan E.; Martínez, Rick A.; Hill, James L.; Weingartner, Herbert; Thompson, Karen; Vitiello, Benedetto; Sunderland, Trey

doi:10.1016/0165-0173(92)90017-g

Cited by 173 publications

(109 citation statements)

References 98 publications

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“…Another muscarinic antagonist, scopolamine, has also been described as inducing cognitive deficits in elderly volunteers (Flicker et al, 1992;Molchan et al, 1992;Ray et al, 1992;Zemishlany and Thorne, 1991), but with some intersubject variability unrelated to pharmacokinetic factors, such as plasma drug level (Tariot et al, 1996). The basis for the intersubject variability in response to anticholinergic treatment is not known, but could reflect individual differences in central cholinergic function or reserve.…”

Section: Introductionmentioning

confidence: 99%

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Pomara

Willoughby

Wesnes³

et al. 2003

Neuropsychopharmacol

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The degree to which elderly adults experience cognitive impairments from centrally acting anticholinergic drugs is variable, but the cause of this variability is unknown. The present study examined the e4 allele as a possible modulator of the effects of trihexyphenidyl hydrochloride (Artane t ), an anticholinergic drug, on memory functioning. Of the 24 cognitively intact, elderly participants (age range 62-76), 12 who possessed the e4 allele, participated in a double-blind, randomized, placebo-controlled, crossover, three-way study. All participants were tested after receiving a single oral dose of trihexyphenidyl (1 or 2 mg) or placebo, with a 7-day washout period between sessions. Memory and psychomotor tests were administered at baseline, and at 1, 2.5, and 5 h post-treatment. Results showed that participants with the e4 allele demonstrated significant impairments in delayed recall after both 1 and 2 mg doses of trihexyphenidyl while the non-e4 group did not. Additionally, while acute administration of the 2 mg dose significantly impaired total recall in both e4 and non-e4 carriers, the e4 carriers showed a more persistent impairment. These findings held when participants with the e2 allele were excluded from the analyses. The e4 groups did not differ with respect to psychomotor performance or plasma drug levels. These results provide evidence suggesting that the e4 allele plays a significant role in increasing cognitive sensitivity to trihexyphenidyl and that a temporal component of memory consolidation may be especially vulnerable. A larger study is warranted to confirm these preliminary findings.

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Section: Introductionmentioning

confidence: 99%

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Pomara

Willoughby

Wesnes³

et al. 2003

Neuropsychopharmacol

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“…The dose of scopolamine was chosen based on a prior study of a range of doses which showed that a statistically signifIcant decline in cognitive test perfor mance in older volunteers occurred at the 0.5 mg dose (Sunderland et al 1986;Molchan et al 1992). In the authors' experience, all subjects administered this dose experience cognitive impairment.…”

Section: Pet Scan Proceduresmentioning

confidence: 99%

“…Most notably, young normal volunteers were studied, and subjects performed a continuous perfor mance task during the scans. Alterations in the choliner gic system have been reported to occur with age that may alter the response to scopolamine in aged subjects (Molchan et al 1992 Cortes et al 1987).…”

Section: Absolute Metabolic Valuesmentioning

confidence: 99%

“…In the authors' experience, all subjects administered this dose experience cognitive impairment. The timing of the scans was based on prior studies showing that the am nestic effects of IV scopolamine occur to a consistent degree 60 to 150 minutes after administration (Sunder land et al 1987;Kopelman and Corn 1988;Molchan et al 1992).…”

Section: Pet Scan Proceduresmentioning

confidence: 99%

“…fNeuropsychopharmacology 10:191-198, 1994J aspects of the memory impairment that occurs in nor mal aging (Drachman and Leavitt 1974;Molchan et al 1992) and Alzheimer's disease (AD) (Sunderland et al 1986; Molchan et al 1992, for review). The pathologi cal changes in the muscarinic cholinergic system of pa tients with AD are thought to contribute to the severe memory impairment that occurs in this disease (Davies and Maloney 1976;Perry et al 1978; Bartus et al 1982; Whitehouse et al 1982).…”

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confidence: 99%

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