Acute Oral Captopril Inhibits Angiotensin Converting Enzyme Activity in Human Cerebrospinal Fluid

Geppetti, Pierangelo; Spillantini, Maria Grazia; Frilli, Stefania; Pietrini, Umberto; Fanciullacci, M; Sicuteri, F

doi:10.1097/00004872-198704000-00004

Cited by 30 publications

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“…However, it is unclear whether and what extent hypotensive effects are due to ACE inhibition within CNS structures. For another ACEI, that is, captopril (217 D, logP 0.3, plasma protein binding 25-30%), which Geppetti showed to inhibit the brain ACE activity in human CSF [10], headache is rare (< 1%) and vertigo is common (< 10%) [12]. There are no studies on ramiprilate concentration or brain ACE activity measurement in human CSF after ramipril administration.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, brain ACE concentrations were found to be reduced in patients with neurodegenerative diseases such as Alzheimer and Parkinson [9]. ACE appeared to originate from the involved regions of the brain and not from the systemic circulation [10]. Due to the presence of potential targets for HCT and ramiprilate in the brain, the current study aimed to investigate, whether these drugs would reach local concentrations at all.…”

Section: Introductionmentioning

confidence: 96%

“…They are often combined to control blood pressure. Central nervous system (CNS) adverse effects (AEs) such as head-DOI: 10.1159/000489999 ache and vertigo are reported albeit rarely for HCT (< 1%) [1] and common (< 10%) for ramipril [2]. This provides indirect evidence that both drugs may reach relevant concentrations in the CNS as a prerequisite for directly causing CNS effects [3].…”

Section: Introductionmentioning

confidence: 99%

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Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System Adverse Effects

et al. 2018

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Background: A drug must reach the central nervous system (CNS) in order to directly cause CNS adverse effects (AEs). Our current study addressed the pharmacokinetic (PK) background of the assumption that CNS concentrations of hydrochlorothiazide (HCT) and ramiprilate may directly cause CNS AEs such as headache and drowsiness. Methods: In neurological patients, paired serum and cerebrospinal fluid (CSF) samples were withdrawn simultaneously. Some of them were treated with HCT (n = 15, daily chronic doses 7.5–25 mg) or ramipril (n = 9, 2.5–10 mg). Total concentrations of HCT and ramiprilate were quantified in these samples. To this end, sensitive liquid chromatography/tandem mass spectrometry methods were developed. Results: CSF reached 4.1% (interquartile ranges 2.5–5%) of total serum concentrations for HCT and 2.3% (1.7–5.7%) for ramiprilate, corresponding to about 11.3% and 5.5% of respective unbound serum concentrations. Conclusion: The PK/Pharmacodynamic characteristics of HCT and ramiprilate in the CNS are unknown. However, since the CSF levels of these agents, both free and bound, were much lower than the corresponding concentrations in serum, it is unlikely that the observed CNS AEs are mediated primarily via direct effects in the brain.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System Adverse Effects

et al. 2018

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“…Некоторые иАПФ, например, периндоприл [142,143], каптоприл [144,145], трандолаприл [146,147], лизиноприл [147], способны проникать через гематоэнцефалический барьер и действовать непосредственно на РАС ЦНС, которая, включая ангиотензины и их рецепторы, вовлечена в процессы, отвечающие за нейропластичность, когнитивную функцию и поведенческие реакции [86,148]. В настоящее время некоторые исследователи склоняются к мысли, что БРА могут эффективнее защищать когнитивную функцию, чем иАПФ, так как, с одной стороны, блокирование АТ 1 Р оказывает антигипертензивное действие (как и в случае применения иАПФ), с другой стороны -происходящее при этом увеличение продукции АII и AIV приводит к стимуляции АТ 2 Р и АТ 4 Р, которые играют существенную роль в поддержании когнитивной функции [149].…”

Section: ангиотензин превращающий фермент и болезнь альцгеймераunclassified

Angiotensin converting enzyme and Alzheimer's disease

Кугаевская

2013

BIOMED KHIM

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Болезнь Альцгеймера (БА) -неизлечимое дегенеративное заболевание центральной нервной системы, приводящее к деменции. В основе БА лежит нейродегенеративный процесс, приводящий к гибели нейронов коры головного мозга, связанный с образованием в мозге нейрофибриллярных клубков и отложением сенильных или амилоидных бляшек, главным компонентом которых является пептид бета-амилоид (Аb). Факторами риска развития БА являются возраст, а также гипертензия, атеросклероз, диабет и гиперхолестеринемия, в патогенез которых вовлечен ангиотензин превращающий фермент (АПФ), ключевой фермент ренин-ангиотензиновой (РАС) и калликреин-кининовой (ККС) систем. Недавно было обнаружено, что АПФ, наряду с другими металлопротеиназами, принимает участие в метаболизме Аb, расщепляя связи на N-концевом и С-концевом участках молекулы Аb. Интерес к роли АПФ в процессах деградации Аb связан с тем, что назначение ингибиторов АПФ (иАПФ) является основным терапевтическим подходом, применяемым при лечении различных форм гипертонии и других сердечно-сосудистых заболеваний. Однако до сих пор не решен вопрос о том, могут ли применяться антигипертензивные препараты, тормозящие РАС, для лечения или предупреждения БА. В настоящее время проводятся многочисленные исследования, посвященные поиску взаимосвязи между РАС и БА.Ключевые слова: болезнь Альцгеймера, пептид бета-амилоид, ангиотензин превращающий фермент, ингибиторы ангиотензин превращающего фермента.ВВЕДЕНИЕ. Болезнь Альцгеймера (БА) -один из наиболее распространенных случаев деменции, составляющий 50-60% от общего числа заболевших. Основным фактором риска развития БА является возраст. Число заболевших существенно растет после 65 лет и приближается к 50% среди людей, достигших 85 лет [1]. Хотя традиционно БА рассматривается 5

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“…The prophylactic activity of captopril was attributed to its capacity to inhibit the degradation of endogen opioids, whose scarcity was considered, at that time, to be the starting point of the migraine crises. The observation that ACE inhibitors operate also in the central nervous system has implied that their prophylactic activity may depend on these central effects [10,11]. Recently, a placebo-controlled clinical study, conducted according to the guidelines of the International Headache Society, has demonstrated the efficacy of lisinopril in prophylactic therapy of migraine [12].…”

Section: Introductionmentioning

confidence: 99%

Arterial hypertension and migraine: comorbidity or something else?

et al. 2004

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IntroductionThe association between arterial hypertension and migraine has been discussed for several years. However, numerous studies that have examined the relationship between these two pathologies have not explained the meaning of their concomitant presence in the same patient. Casual association between arterial hypertension and migraineNumerous studies on patients observed in headache centers show an association between headache (including migraine) and arterial hypertension [1,2]. As both these pathologies have an elevated prevalence in the general J Headache Pain (2004) Abstract Several studies on patients observed in headache centers show an association between headache, including migraine, and arterial hypertension. As both these pathologies have an elevated prevalence in the general population, their association in the same patient could be casual and does not indicate a real comorbidity. Recent studies undertaken on the general population show results that seem to exclude a comorbidity between the two pathologies. Basal elevated diastolic and systolic pressures are not associated to the emergence of a migraine, whereas for subjects with systolic pressure over 150 mmHg, the risk of developing a nonmigrainous headache is less than 30% compared with normotensive subjects. However, other recent studies suggest that the association between arterial hypertension and migraine consists in the sharing of genetic abnormalities involving the angiotensin-converting enzyme (ACE): a greater availability of angiotensin II, due to a higher activity of ACE, seems to be a pathogenetic mechanism common to arterial hypertension and migraine. The possible pathogenetic role of ACE in migraine and in other headaches seems to be confirmed by several clinical studies that show the efficacy of drugs that inhibit ACE or block angiotensin II receptor. Recent prospective studies have evaluated risk factors for the chronicity of episodic migraine and have shown that arterial hypertension appears to play an important role because a higher incidence of this disease has been observed in patients with episodic migraine transformed into chronic type.

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Acute Oral Captopril Inhibits Angiotensin Converting Enzyme Activity in Human Cerebrospinal Fluid

Cited by 30 publications

References 0 publications

Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System Adverse Effects

Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System Adverse Effects

Angiotensin converting enzyme and Alzheimer's disease

Arterial hypertension and migraine: comorbidity or something else?

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