The effect of Acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal cerebral ischaemia

Abstract

The purpose of the present study was to examine the effect of Acetylcholinesterase inhibitor (AChEI) on r-CBF (group A) and its protecting effect on focal ischaemic cell damage (group B). The pial arterial diameter and the r-CBF were measured with a width analyzer and with a laser Doppler flowmeter through a cat cranial window on the ectosylvian gyrus. The ischaemic area was measured histologically. We used intravenous injection of AChEI([-])(S)-N-ethyl-3-[(1-dimethyl- amino)ethyl]-N-methyl-phenylcarbamate, SDZENA 713, Sands Pharmacy) to block AChE. Twenty minutes after injection AChEI (0.6 mg/kg) the pial arteriole dilated 108.5 +/- 1.8% and the r-CBF increased 115.4 +/- 2.6%. The pial arteriole dilated maximally to 137.6 +/- 6.5% at 120 minutes after injection and the r-CBF increased maximally to 137.1 +/- 19.5% at 60 minutes after injection. The protecting effect was evaluated using cats and 1 hour of occlusion of the middle cerebral artery (MCA). Twenty minutes after injection of AChEI, the pial arteriole dilated to 116.7 +/- 2.4% and the r-CBF increased to 111.9 +/- 2.6% significantly. During MCA occlusion the r-CBF decreased to 24.7-41.4% in group B and 25.1-32.6% in sham group (group C). The pial arteriole dilated 145.0-184.0% in group C and 150.7-171.6% in group B during MCA occlusion and 30 minutes after reperfusion the pial arteriole returned to 120.0 +/- 3.3% in group C and 123.4 +/- 11.3% in group B. There were no significant changes in the r-CBF and the vessel diameter between group B and C during the 2 hours after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Targeting acetylcholinesterase and butyrylcholinesterase in dementia

“…In animal models, ChE-Is induce vascular relaxation and improve CBF in the ischaemic brain (Sadoshima et al, 1995 ;Tanaka et al, 1994Tanaka et al, , 1995Tsujimoto et al, 1993). Furthermore, treatment with ChE-Is may prevent cholinergic deficits and reduce pyramidal cell loss in ischaemic hippocampus (Tanaka et al, 1994(Tanaka et al, , 1995.…”

Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine

“…Furthermore, Rivastigmine resulted in overall clinical improvement in patients with vascular dementia which is similar to AD [27][28]. In vivo experiments showed that SDZ ENA 713, a racemate of Rivastigmine improved cerebral blood flow, reduced blood vessel damage and ischaemic cell damage [29]. In addition, switching from Donepezil to Rivastigmine when patients don't respond to Donepezil treatment is effective in 55% of cases [30].…”

“…Additional experiments were carried out to determine the possibility that Donepezil or Rivastigmine might have modulated the vascular activity of 1µM Aβ [25][26][27][28][29][30][31][32][33][34][35] or 0.1µM Aβ 1-40 and the subsequent response to acetylcholine or bradykinin via a direct action on the smooth muscle cell function. In these experiments, rats were perfused with Ringer's solution to stabilise the baseline, followed by 10 min perfusion of 100µM sodium nitroprusside, followed by 20 min perfusion of Ringer's solution to restabilise the baseline.…”

“…To examine the effect of acetylcholine or bradykinin on the microvasculature in the control group, acetylcholine at 100µM or bradykinin at 1µM were perfused for 30 min over the blister base. The effect of Aβ [25][26][27][28][29][30][31][32][33][34][35] or Aβ 1-40 on the vascular response to acetylcholine (100µM) was examined by perfusing Aβ 25-35 (1µM) or Aβ 1-40 (0.1µM) for 10 min followed immediately by perfusing 100µM of acetylcholine for 30 min. A similar protocol was used to test the effect of 0.1µM Aβ 1-40 on the vascular response to bradykinin (1µM).…”

Is rivastigmine safe as pretreatment against nerve agents poisoning? A pharmacological, physiological and cognitive assessment in healthy young adult volunteers

“…It is approved for the treatment of mild to moderate dementia of the Alzheimer's type (AD) and dementia related to Parkinson's disease (Corey-Bloom et al, 1998;Emre et al, 2004;Finkel, 2004;Rö sler et al, 1998Rö sler et al, , 1999. Rivastigmine was also found effective in counteracting cognitive damage following traumatic brain injury and focal ischemia in both animal and human (Chen et al, 1998a(Chen et al, , 1998bCummings, 2000;Giladi et al, 2003;McKeith et al, 2000;Moretti et al, 2001;Silver et al, 2009;Tanaka et al, 1995;Tsujimoto et al, 1993;Wesnes et al, 2002), and was tested for its effects against cognitive deterioration in schizophrenia and drug abuse (Ribeiz et al, 2010;Sofuoglu, 2010;Theunissen et al, 2015). In animal studies, pretreatment with central ChE inhibitors were repeatedly demonstrated to protect against OP nerve agents induced damage (Albuquerque et al, 2006;Alexandrova et al, 2014;Grunwald et al, 2002;Haug et al, 2007;Harris et al, 1991;Janowsky et al, 2004Janowsky et al, , 2005Lallement et al, 2001;Philippens et al, 2000).…”