Linopirdine (DUP 996): Cholinergic Treatment of Older Adults Using Successive and Non-successive Tests

Abstract

The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.

Voltage-gated potassium channels as therapeutic targets

“…5) demonstrated improvements in learning and memory performance in animals154. However clinical trials only provided equivocal results for treating cognitive disorders155. While second generation inhibitors like XE-991 ( 30 ) and DMP-543 ( 31 ) were developed156, no further clinical efficacy studies investigating improvement of cognitive function have been reported.…”

K+ Channel Modulators for the Treatment of Neurological Disorders and Autoimmune Diseases

“…94 Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive 95 or showed that it did not improve memory performance in elderly subjects, 96 linopirdine became a valuable pharmacological tool. In 1995 Aiken et al reported that linopirdine blocks the M-current in rat CA1 pyramidal neurons and suggested that the I M blockade might be responsible for the enhancement of neurotransmitter release by linopirdine because the two effects had similar IC 50 /EC 50 values.…”

Cardiovascular KCNQ (Kv7) Potassium Channels: Physiological Regulators and New Targets for Therapeutic Intervention

“…Linopirdine was tested in clinical trials with the hope that it would reverse age-associated memory impairment or the cognitive deficit in patients with Alzheimer's disease (AD). Unfortunately, very little clinical benefit of linopirdine has been observed so far (Rockwood et al, 1997;Börjesson et al, 1999).…”