The effects of ACE inhibitors captopril and SQ29,852 in rodent tests of cognition

Costall, B.; Coughlan, J.; Horovitz, Zola P.; Kelly, M.E.; Naylor, R.J.; Tomkins, D.M.

doi:10.1016/0091-3057(89)90390-0

Cited by 89 publications

(36 citation statements)

References 10 publications

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“…To assess the level of anxiety in rSey 2 /+ rats, we next carried out a light-dark (LD) choice test [33]. rSey 2 /+ rats spent more time in the light side of the test box than that WT did (two-way ANOVA with repeated measures (genotype 6 time); main effect of factor 'genotype': F(1) = 7.06, P,0.02; Fig.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Pax6 mutant rat as a model for autism

Osumi

2011

Neuroscience Research

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Section: Resultsmentioning

confidence: 99%

Evaluation of Pax6 mutant rat as a model for autism

Osumi

2011

Neuroscience Research

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“…Costall et al, 1989), it is of particular interest that neither the present study nor those of Lichter et al (1986) or Deary et al (1991) showed any specific benefit of this class of drug in hypertensive patients. However, effects on memory in normal human subjects have not been found consistently (e.g.…”

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confidence: 88%

The effects of anti‐hypertensive medication on learning and memory.

Powell

Pickering

Wyke

et al. 1993

Brit J Clinical Pharma

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1 The aim of the study was to investigate whether there were differential effects of three different anti-hypertensive medications (cilazapril, atenolol, nifedipine) on cognitive function. 2 A sub-group of patients participating in a large clinical trial of these three drugs, randomly allocated between the three drug conditions, received cognitive assessment at two points before the commencement of treatment and then after 12 and 24 weeks of treatment. Seventy-six patients began treatment, and 55 completed the full course. 3 Tests of learning and memory were designed specially for the study, with a different but comparable version administered on each assessment occasion, in a fixed order. 4 No significant differences between drug groups were found in any index of learning or memory, at any testing occasion. The results were the same whether or not treatment non-completers were included in the analysis.

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“…Even modest differences among ACE inhibitors with regard to accumulation within the kidney could be important, since a complete block of the intrarenal renin-angiotensin system can decrease glomerular filtration and lead to kidney failure, particularly in patients with already compromised renal function Swales, 1987 (van Nispen & Pinder, 1987). SQ 29,852, which we have shown to have a significant but delayed distribution into the brain, has been shown to be exceptionally potent for improving performance in rodent models of cognition (Costall et al, 1989), a phenomenon that has also been observed with an analog of ramipril (Usinger et al, 1988). It is important to further investigate the localization of ACE inhibitors within the brain.…”

Section: Preparation Of Uncentrifuged Homogenates Of Tissuesmentioning

confidence: 99%

Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE).

Dw¹,

Wang²,

Fung³

et al. 1989

Brit J Clinical Pharma

108

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1. Seven drugs (captopril, zofenopril, enalapril, ramipril, lisinopril, fosinopril, and SQ 29,852) were compared in vitro in homogenates of aorta, brain, heart, lung, and kidney and in sera of spontaneously hypertensive rats (SHR) both with respect to potencies of their active moieties as inhibitors of angiotensin‐converting enzyme (ACE), and, where applicable, rates of hydrolysis of their prodrug ester functions. 2. In ex vivo dose‐response and time‐course studies, the inhibitory effects of the seven drugs on tissue ACEs and their relative distributions to SHR tissues were compared following oral administration. 3. The relative potencies of the inhibitory moieties of the drugs (in parentheses) and the normalized ‘equiactive’ oral doses employed for time‐course studies were: SQ 29,852 (1.0), 100 mg kg‐1; captopril (3.5), 30 mg kg‐1; enalapril (12), 20 mg kg‐1; fosinopril (13), 25 mg kg‐1; zofenopril (20), 10 mg kg‐1; lisinopril (24), 10 mg kg‐1; and ramipril (51), 5 mg kg‐1. 4. Following oral administration of the drugs to SHR, the degree and duration of ACE inhibition in aorta and lung correlated with the antihypertensive actions, with ramipril, lisinopril, and zofenopril producing effects of the greatest magnitude and duration. 5. Ramipril and enalapril did not inhibit brain ACE ex vivo; captopril and zofenopril had modest but short‐lasting effects; and fosinopril, lisinopril, and SQ 29,852 had long‐lasting inhibitory actions, which, with the latter two, were delayed in onset. 6. All of the drugs produced significant inhibition of kidney ACE, with ramipril and fosinopril having somewhat weaker effects, perhaps due to biliary routes of excretion. 7. Captopril, fosinopril, and particularly zofenopril inhibited cardiac ACE ex vivo with degrees and durations that were marked compared with those of the other drugs; preliminary studies with isolated hearts suggest a possible relationship between inhibition of cardiac ACE and preservation of cardiac function subsequent to ischaemia.

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The effects of ACE inhibitors captopril and SQ29,852 in rodent tests of cognition

Cited by 89 publications

References 10 publications

Evaluation of Pax6 mutant rat as a model for autism

Evaluation of Pax6 mutant rat as a model for autism

The effects of anti‐hypertensive medication on learning and memory.

Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE).

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