Physostigmine and Arecoline: Effects of Intravenous Infusions in Alzheimer Presenile Dementia

Christie, J. E.; Shering, A.; Ferguson, James M.; Glen, A.I.M.

doi:10.1192/bjp.138.1.46

Cited by 347 publications

(90 citation statements)

References 24 publications

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“…Early studies of the cholinesterase inhibitor physostigmine observed significant drug-induced improvement in humans in long-term memory of words (Davis et al, 1978), in picture recognition (Christie et al, 1981), and significant dose-dependant improvement in aged monkeys in recent visual memory (Bartus and Uehara, 1979). More recently, physostigmine administration has changed the level of arousal and selective attention to visual tasks in pattern-flash stimulus tests in human PET studies of elderly subjects (Mentis et al, 2001).…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Mumenthaler

Yesavage

Taylor

et al. 2003

Neuropsychopharmacol

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The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine) ¼ 0.80; ES (donepezil) ¼ 1.02; ES (alcohol acute) ¼ À3.66; ES (alcohol 8 h) ¼ À0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

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Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Mumenthaler

Yesavage

Taylor

et al. 2003

Neuropsychopharmacol

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“…These include such natural agents as arecoline (Christie et al, 1981) and pilocarpine (Caine, 1980), and synthetic compounds such as RS-86 (Mouradian et al, 1988). Clinical trials with such agents have generally been disappointing, at least partly due to the side effects associated with muscarinic receptor stimulation.…”

Section: Introductionmentioning

confidence: 99%

A novel series of non‐quaternary oxadiazoles acting as full agonists at muscarinic receptors

Freedman¹,

Harley

Patel

et al. 1990

British J Pharmacology

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1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors.2 These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 5 The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6 These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.

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“…A variety of inhibitors of cholinesterase have been used in these treatments, including physostigmine (Christie et al, 1981) and tetrahydroaminoacridine (Summers et al, 1986) for treatment of Alzheimer's patients. Since in these diseases the therapeutic aim is to increase the action of acetylcholine it might be counterproductive to use an acetylcholinesterase inhibitor which also depresses acetylcholine action at the level of the nicotinic cholinoceptor, although the importance of nicotinic receptor activation in the central effects of acetylcholinesterase inhibitors is unclear.…”

Section: Differences In the Action Between The Cholinesterase Inhibitorsmentioning

confidence: 99%

Electrophysiological estimation of the actions of acetylcholinesterase inhibitors on acetylcholine receptor and cholinesterase in physically isolated Aplysia neurones

Oyama

Hori

Evans

et al. 1989

British J Pharmacology

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1 The actions of representative cholinesterase inhibitors on the acetylcholine responses of physically isolated single neurones from the pedal ganglion of Aplysia californica were studied, using electrophysiological techniques and rapid agonist application to analyse both the inhibitory actions on the acetylcholine receptor-channel complex and the degree of inhibition of acetylcholinesterase activity on the same neurone. The inhibitors used were physostigmine, edrophonium and diisopropylfluorophosphate (DFP). 2 When selected neurones were suddenly exposed to 50 JM acetylcholine by a 'concentration clamp' technique a large Na-dependent inward current was initiated, and decayed in the continued presence of acetylcholine without external perfusion. However, if perfusion of the acetylcholine solution was reinitiated the current increased somewhat, indicating that the decay of current was due to some combination of receptor desensitization and local depletion of acetylcholine at the membrane by acetylcholinesterase. 3 With simultaneous application of acetylcholine (50!M) and physostigmine (0.1 to 100l M) there was a dose-dependent reduction of peak amplitude of the acetylcholine response. However, physostigmine at low concentrations (0.1 to 10.uM) caused a time-dependent increase in the current amplitude alone with a time-and dose-dependent inhibition of acetylcholinesterase activity. At the highest concentration of physostigmine (100 uM) acetylcholinesterase activity was abolished but the current peak was very depressed. After removal of physostigmine from the bathing solution, the current amplitude decreased toward the control at the two lower concentrations as the inhibitory actions on acetylcholinesterase activity were almost reversible, while at the two higher concentrations (10 and 100pM) the current increased and the inhibition of acetylcholinesterase remained. 4 When acetylcholine (50pM) and edrophonium (0.1 to 10pM) were applied simultaneously, edrophonium caused a dose-dependent increase in the peak amplitude that was correlated with a dosedependent inhibition of acetylcholinesterase activity. Prolonged exposure to edrophonium did not change the peak amplitude and there was no time-dependent change in the inhibition of acetylcholinesterase activity. At the highest concentration of edrophonium used (100pM), simultaneous application with acetylcholine augmented the peak amplitude relative to control, but to a lesser extent than 10 gM. Prolonged exposure to the highest concentration of edrophonium caused a timedependent reduction in the peak amplitude. The effects of edrophonium were quickly reversible after the removal of the drug from the bathing solution. 5 DFP (1 and 10mM), similar to 1OOpM physostigmine, caused a dramatic reduction of the peak current on simultaneous application with ftetylcholine. During exposure to DFP the current amplitude and acetylcholinesterase activity were very depressed. After removing DFP from the bathing solution the current amplitude increased to more than the control level a...

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Physostigmine and Arecoline: Effects of Intravenous Infusions in Alzheimer Presenile Dementia

Cited by 347 publications

References 24 publications

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

Psychoactive Drugs and Pilot Performance: A Comparison of Nicotine, Donepezil, and Alcohol Effects

A novel series of non‐quaternary oxadiazoles acting as full agonists at muscarinic receptors

Electrophysiological estimation of the actions of acetylcholinesterase inhibitors on acetylcholine receptor and cholinesterase in physically isolated Aplysia neurones

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