Cicletanide Improves Outcome After Left Circumflex Coronary Artery Occlusion-Reperfusion in the Dog

Jouve, R; Langlet, F; Puddu, Paolo Emilio; Rolland, Pierre H.; Guillen, Jean-Claude; Cano, J. P.; Serradimigni, A

doi:10.1097/00005344-198601000-00030

Cited by 21 publications

(11 citation statements)

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“…This peripheral anti-HI component of cicletanine action could have been partially responsible for the direct vas- cular effect of cicletanine. In dogs with coronary ischemia its anti-Hl action may have been responsible for the protection from ventricular arrhythmias (20).…”

Section: Interactions With Histamine Receptorsmentioning

confidence: 99%

Cicletanine

Chabrier

Guinot

Tarrade

et al. 1988

Cardiovascular Drug Reviews

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Cicletanine hydrochloride is a new antihypertensive molecule synthetized and studied in our laboratory. Its chemical structure is uncommon for an antihypertensive molecule; it is characterized by the presence of a furopyridine group. Cicletanine is, therefore, a member of a new family of compounds with primarily antihypertensive properties, although some of the furopyridine derivatives have also antiallergic and antiinflammatory effects.The mechanism by which cicletanine lowers blood pressure has not been definitively established, although it appears to differ from that of other classes of antihypertensive drugs. Cicletanine acts on vascular smooth muscle by increasing prostacyclin synthesis and by interacting either directly with cytosolic Ca2+ pools or indirectly through various agents capable of mobilizing intracellular Ca ' ' , e.g., histamine.Studies in animals and humans demonstrated that the antihypertensive effect of cicletanine is clearly dissociable from its renal effect, which can be seen only at highdose levels of the drug.Clinical trials have confirmed the efficacy and safety of cicletanine in the treatment of hypertension, both as monotherapy or in combination with other antihypertensive drugs. CHEMISTRYCicletanine was synthetized by Esanu et al. (9) in the research laboratories of Institute Henri Beaufour, Le Plessis-Robinson (France). It was selected from a large number of furopyridines for its specific antihypertensive activity and very low, if any, toxicity. The chemical structure of cicletanine ( HCl) : (-+ ) 3-(4-chloropheny1)-1,3dihydro-7-hydroxy-6-methyl furo[3,Cc]pyridine is shown in Fig. 1. Its chemical synthesis from 2-,2,8-trimethyl-5-formyl pyrido [ 4,3-el 1,3-dioxine has been described (9). Cicletanine HC1 has a molecular weight of 298.2. It is not soluble in 166 CICLE TANINE 167 water, but soluble in ethanol and dimethyl sulfoxide. It is a white crystalline powder with a melting point of 2 19-228°C. PHARMACOLOGY Effect on Blood PressureThe activity of cicletanine on blood pressure was evaluated in anesthetized normotensive rats and dogs and in several models of hypertensive rats: desoxycorticosterone acetate, spontaneously ( SH ) and stroke-prone spontaneously ( SH-SP) hypertensive rats and rats with stress-induced hypertension.In the anesthetized normotensive rat, cicletanine, administered orally at 100 and 300 mg/kg, did not affect either mean blood pressure or heart rate. The blood pressure effects of epinephrine, norepinephrine, acetylcholine, isoproterenol, or serotonin were not altered by pretreatment with cicletanine.The effect of intravenously injected cicletanine on the main hemodynamic cardiovascular parameters-systolic and diastolic aortic pressure, heart rate, aortic blood flow, coronary (circumflex artery) and femoral arterial blood flow-were studied in anesthetized normotensive dog. At doses higher than 5 mg/kg i.v., cicletanine produced only a slight and transient bradycardia, a minor reduction of systolic arterial pressure, and a brief decrease in diastolic pressure. F...

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Section: Interactions With Histamine Receptorsmentioning

confidence: 99%

Cicletanine

Chabrier

Guinot

Tarrade

et al. 1988

Cardiovascular Drug Reviews

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“…Numerous studies have been performed illustrating either the antiarrhythmic or the antiischemic effect of the drug in in vitro and ex vivo models 7,31 or whole animals, 10,11 but to the best of our knowledge, this is the first work, which demonstrates the cardioprotective action of CIC in a preclinical model, which exposes several leading symptoms (ie, insulin resistance, dyslipidemia, hypertension) of MS. Moreover, the animals were conscious throughout the entire set of experiments; therefore, the examined effects of CIC were influenced neither positively nor negatively by the untoward actions of drugs applied for anesthesia induction and maintenance.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] On the other hand, very few studies concerning CIC's antiarrhythmic action were carried out under in vivo conditions. 10,11 Moreover, in these latter experiments, arrhythmias were induced exclusively by the method of ischemia/reperfusion, not programmed electrical stimulation (PES).…”

Section: Introductionmentioning

confidence: 99%

Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

Drimba

Hegedűs²,

Yin³

et al. 2012

Journal of Cardiovascular Pharmacology

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“…Primary consideration in these studies was given to the older findings relating to the diuretics or ACE inhibitors, as these lead more frequently than any other group of agents to stimulation of prostacyclin synthesis. Persistent increase in renal prostacyclin excretion in healthy subjects after 150 mg cicletanine orally (x ± SD) [98] of the arachidonic acid cascade with increased liberation of cyclooxygenase products [37,50,82,98,128]. A new substance has now been successfully developed which produces stimulation of prostacyc1in synthesis in vivo persisting for several hours (Fig.…”

Section: Prostacyc6n-stimulating Substancesmentioning

confidence: 99%

Prostacyclin and Hypertension

Bönner¹,

Rahn²

1990

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Cicletanide Improves Outcome After Left Circumflex Coronary Artery Occlusion-Reperfusion in the Dog

Cited by 21 publications

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Cicletanine

Cicletanine

Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

Prostacyclin and Hypertension

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