Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden

Abstract

Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer’s disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as different cognitive deficit models. Scopolamine may model more advanced stages of Alzheimer’s disease whereas biperiden may model the early deficits in declarative memory in aging and mild cognitive impairment.

Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review

“…As mentioned, biperiden is an M 1 mAChR preferring antagonist, and cognitive impairment results suggest that down-regulation of the M 1 receptor could be a significant contributor to cognitive symptoms of schizophrenia. Although scopolamine has been used to generate “cognitive dysfunction”, it has been observed that, along with cognitive dysfunction, scopolamine also produces impairment in attention and motivation [ 114 ]. This effect is due to the non-selective nature of scopolamine.…”

“…Based on these findings, it was proposed that scopolamine could be used to model cognition dysfunction in AD. Notably, biperiden could be a “cleaner” way to develop a “cholinergic deficit model of cognitive dysfunction” [ 114 ]. Previous literature indicates that cognitive impairment may be a vulnerability marker for psychotic disorders as it is also observed in healthy people with high genetic risk [ 115 ].…”

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

“…It was approved by the FDA in 1959 in treating PD, and it acts by antagonizing the Ach effect on the muscarinic receptors. 190 Moreover, biperiden is effective in treating acute brain injury and post‐traumatic epilepsy through modulation of BDNF signalling. 191 Zhou et al.…”

“…It was approved by the FDA in 1959 in treating PD, and it acts by antagonizing the Ach effect on the muscarinic receptors. 190 Moreover, biperiden is effective in treating acute brain injury and post-traumatic epilepsy through modulation of BDNF signalling. 191 Zhou et al 191 found that biperiden has antidepressant-like effects in mice by increasing the expression of BDNF signalling in the prefrontal cortex and hippocampus.…”

“…Biperiden is an anti‐muscarinic drug that treats movement disorders such as rigidity and to a lesser extent tremor in PD, but not for tardive dyskinesia. It was approved by the FDA in 1959 in treating PD, and it acts by antagonizing the Ach effect on the muscarinic receptors 190 . Moreover, biperiden is effective in treating acute brain injury and post‐traumatic epilepsy through modulation of BDNF signalling 191 .…”