Receptor interaction profile and CNS general pharmacology of metrifonate and its transformation product dichlorvos in rodents

Hinz, Volker; Blokland, Arjan; Staay, Franz-Josef van der; Gebert, Irmingard; Schuurman, T.; Schmidt, Bernard

doi:10.1002/(sici)1098-2299(199605)38:1<31::aid-ddr4>3.0.co;2-m

Cited by 16 publications

(6 citation statements)

References 43 publications

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“…Only a slight interaction of DDVP with the nicotine receptor binding site (35 %) was observed (23). This finding supports the assumption that the therapeutic effect of metrifonate is mediated primarily through a selective activation of the cholinergic system (32).…”

Section: In Vitro Studiessupporting

confidence: 80%

“…Metrifonate and DDVP do not bind to 61 out of 62 mammalian neurotransmitter receptor subtypes, neuropeptide receptors, or ion channel binding sites investigated (23). Only a slight interaction of DDVP with the nicotine receptor binding site (35 %) was observed (23). This finding supports the assumption that the therapeutic effect of metrifonate is mediated primarily through a selective activation of the cholinergic system (32).…”

Section: In Vitro Studiessupporting

confidence: 54%

“…Neither metrifonate nor DDVP show analgesic effects or effects on motor coordination; these agents shorten duration of hexobarbital-induced anaesthesia, lower body temperature, and do not show convulsive effects in rodents (23).…”

Section: Effects On Memory Learning and Behaviormentioning

confidence: 87%

Section: In Vitro Studiesmentioning

confidence: 91%

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Metrifonate: A Cholinesterase Inhibitor for Alzheimer's Disease Therapy

Schneider

Giacobini

1999

CNS Drug Reviews

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Section: In Vitro Studiessupporting

confidence: 80%

Section: In Vitro Studiessupporting

confidence: 54%

Section: Effects On Memory Learning and Behaviormentioning

confidence: 87%

Section: In Vitro Studiesmentioning

confidence: 91%

See 2 more Smart Citations

Metrifonate: A Cholinesterase Inhibitor for Alzheimer's Disease Therapy

Schneider

Giacobini

1999

CNS Drug Reviews

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“…The lack of a difference in UR amplitudes between metrifonate-treated subjects and control subjects indicated that metrifonate did not induce an increase in sensitivity to the US. Administration of metrifonate in this study did not result in cholinergic side effects such as fasciculations, tremor, facial clonus, or increased defecation (Bignami et al, 1975; Blokland et al, 1995; Hinz, Blokland, et al, 1996).…”

Section: Resultsmentioning

confidence: 60%

Metrifonate improves associative learning and retention in aging rabbits.

Kronforst-Collins¹,

Moriearty²,

Schmidt³

et al. 1997

Behavioral Neuroscience

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The cholinergic system is known to show deterioration during aging and Alzheimer's disease (AD). In response, a therapeutic approach to AD has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase (ChE) inhibitors. In this study treatment with the long-lasting ChE inhibitor metrifonate facilitated acquisition and retention of eyeblink conditioning in aging rabbits. Metrifonate treatment resulted in steady-state, dose-dependent acetylcholinesterase (AChE) inhibition in red blood cells. Maximal behavioral efficacy was achieved with AChE inhibition of approximately 40%, with no further improvements resulting from increased levels of inhibition. Metrifonate was behaviorally effective in the absence of the severe side effects that can plague ChE inhibitors, supporting metrifonate as a possible treatment for the cognitive deficits resulting from normal aging and AD.

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