Pressor and bradycardic effects of tacrine and other acetylcholinesterase inhibitors in the rat

Lazartigues, Eric; Freslon, Jean‐Louis; Tellioǧlu, Tahir; Brefel‐Courbon, Christine; Pelat, Michel; Tran, Marie-Antoinette; Montastruc, Jean‐Louis; Rascol, Olivier

doi:10.1016/s0014-2999(98)00717-1

Cited by 29 publications

(20 citation statements)

References 31 publications

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“…It also produces a corresponding bradycardia, which may be a direct peripheral effect of tacrine or a product of the baroreflex [28]. The central pathway leading to hypertension is mediated predominantly by central M2 cholin-ergic receptors [29], probably leading to increased vasopressin, adrenaline and noradrenaline release [27]. We would hypothesise that the overall reduction in HRV, with a change in spectral powers towards low frequency predominance associated with donepezil, is the result of central stimulation of sympathetic efferent mechanisms more 'powerful' than the peripheral vagotonic influences.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Donepezil in Patients with Dementia

McLaren

Allen

Murray

et al. 2003

Dement Geriatr Cogn Disord

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Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer’s disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms²; p = 0.001) but also for total power (median changed from 1,563 to 844 ms²; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Donepezil in Patients with Dementia

McLaren

Allen

Murray

et al. 2003

Dement Geriatr Cogn Disord

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“…The observed difference in cholinergic mechanisms mediating the pressor effect of peripherally or centrally administered THA could be due to the difference in concentration achieved in brain tissue after administration of drugs. The central involvement of muscarinic cholinergic receptors in the THA-induced pressor effect has been shown in previous investigations on centrally [19] and peripherally [20,21] injected THA in normotensive animals. On the other hand, it has been previously shown that the central nicotinic receptors are involved in the pressor effects of cholinomimetic drugs such as oxotremorine, physostigmine [7] or choline [9] in haemorrhaged hypotensive rats.…”

Section: Discussionmentioning

confidence: 52%

“…It has been used for the treatment of Alzheimer's disease and has recently been marketed in the USA and several European countries for this purpose. Recent studies have shown that both centrally injected [19] and peripherally administered THA [20,21] can increase blood pressure in conscious normotensive animals. Our findings, taken with the reports implicating the importance of the brain cholinergic tone in hypotension and shock, suggested that THA, by increasing central cholinergic transmission indirectly, is likely to reverse hypotension and increase survival under several shock conditions.…”

Section: Introductionmentioning

confidence: 99%

Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine

Savci¹,

Çavun²,

Gurun³

et al. 2001

Pharmacology

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The cardiovascular effects of tetrahydroaminoacridine (tacrine; THA) were investigated in haemorrhaged rats. Intracerebroventricular (i.c.v.) injection of THA (10, 25 and 50 µg) restored blood pressure in a dose- and time-dependent manner. Atropine (10 µg, i.c.v.), a muscarinic receptor antagonist, attenuated the pressor response to THA (25 µg, i.c.v.), while mecamylamine (50 µg, i.c.v.), a nicotinic receptor antagonist, caused only a slight blockade in the pressor effect of THA. Simultaneous pretreatment with atropine and mecamylamine almost abolished the blood pressure effect of i.c.v. THA (25 µg). Haemorrhage increased plasma levels of adrenaline, noradrenaline, vasopressin and plasma renin activity. THA (25 µg, i.c.v.) administration caused additional increases in vasopressin and adrenaline levels but not of renin activity and noradrenaline levels. The reversal of hypotension by THA was greatly attenuated by administration of either prazosin, an α₁-adrenoceptor antagonist (0.5 mg/kg, i.v.) or by the vasopressin V₁ receptor antagonist [β-mercapto-β,β-cyclopenta-methylenepropionyl¹, O-Me-Tyr²-Arg⁸]-vasopressin (10 µg/kg, i.v.). Pretreatment of rats with both prazosin and the vasopressin antagonist simultaneously completely inhibited the pressor response. Intravenous administration of THA (1, 1.5 and 3 mg/kg) also reversed hypotension in rats. Atropine (10 µg, i.c.v.) greatly attenuated the pressor response to THA (1.5 mg/kg, i.v.), while mecamylamine (50 µg, i.c.v.) failed to change the pressor effect of THA. In anaesthetised haemorrhaged rats, THA (1.5 mg/kg, i.v.) increased blood pressure and survival time of the animals. These results show that centrally and peripherally injected THA reverses haemorrhagic hypotension and increases survival time in rats. Activation of central muscarinic and nicotinic receptors is involved in the pressor response to i.c.v. THA. The pressor effect of i.v. THA is solely mediated by central muscarinic receptors. Moreover, the increase in plasma adrenaline and vasopressin levels appears to be involved in the pressor effect of THA.

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“…Pyridostigmine, like neostigmine, does not cross the blood-brain barrier. Therefore, its cardiovascular effects cannot be due to stimulation of central cholinergic systems [6].…”

Section: Pyridostigmine In the Treatment Of Orthostatic Hypotensionmentioning

confidence: 99%

“…As reported by Sandroni et al in patients with autonomic failure, no changes in resting blood pressure were observed in healthy humans. Acute administration in healthy subjects lowers heart rate and enhances cholinergic cardiac activation [6][7][8]. Of course, one should take into consideration that the response may differ in controls and autonomic failure patients.…”

Section: Pyridostigmine In the Treatment Of Orthostatic Hypotensionmentioning

confidence: 99%

Pyridostigmine in the treatment of orthostatic hypotension

Senard

2005

Clin Auton Res

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Pressor and bradycardic effects of tacrine and other acetylcholinesterase inhibitors in the rat

Cited by 29 publications

References 31 publications

Cardiovascular Effects of Donepezil in Patients with Dementia

Cardiovascular Effects of Donepezil in Patients with Dementia

Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine

Pyridostigmine in the treatment of orthostatic hypotension

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