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Aim: Physicochemical and pharmacological study of the supramolecular inclusion complexes of the hypotensive drug nifedipine (NF) with the larch polysaccharide arabinogalactan (AG). Materials & methods: The NF:AG complexes were obtained and their physicochemical properties were studied. Their hypotensive action and pharmacokinetic profiles were evaluated in rats with normal and elevated arterial blood pressure. Results: In both rat lines the NF:AG complex decreased the arterial blood pressure at a lower dose than free NF (1.75 mg/kg of NF in complex compared with 3.5 mg/kg of free NF) and has a better pharmacokinetic profile than free NF. Conclusion: The use of the NF:AG complex is an effective way to sufficiently enhance and hasten NF’s hypotensive action.

Hyeong Jin Lee,1,* Bongjin Lee,2,* June Dong Park,2 Hyung Joo Jeong,2 Yu Hyeon Choi,2 Hee Young Ju,1 Che Ry Hong,1 Ji Won Lee,1 Hyery Kim,1 Dong In Suh,3 Kyung Duk Park,1 Hyoung Jin Kang,1 Hee Young Shin,1 Hyo Seop Ahn1 1Department of Pediatrics, Cancer Research Institute, 2Division of Pediatric Intensive Care, Department of Pediatrics, 3Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea *These authors contributed equally tothis work Purpose: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.Materials and methods: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20%) drops.Results: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P

Diseases of the cardiovascular system is often accompanied by other serious diseases – it called polymorbidity. In such cases it is necessary to carefully select drugs for treatment, paying particular attentiong to their influence on each other in the human organism, efficiency of their simultaneous appointment and safety against side effects. For the treatment of hypertension successfully used angiotensin receptor blockers II, which have proven to be effective antihypertensive drugs with additional therapeutic properties. Among the other members of the group candesartan (Candesar, SUN pharma company) gained recognition among doctors thanks to the good performance of lowering blood pressure, as well as the additional effects, such as: nefroprotection, improvement current diabetes and even prevent further his case, antiatherosclerotic action. Candesartan acts as an effective hypotensive drug, which is also capable of preventing the development of hypertension, in addition shows good results with regard to increasing the duration of life of the patients and improve the prognosis of cardiovascular diseases. The accumulated evidence base and years of experience in the use clinicians confirm efficacy and safety of candesartan in patients with polymorbidity.

OBJECTIVES: To determine whether hypotensive drugs may play a pivotal role in inducing orthostatic hypotension (OH)-related syncope. DESIGN: Prospective, observational, multicenter study. SETTING: Acute care wards, syncope units, and centers for the diagnosis of dementia. PARTICIPANTS: Individuals aged 65 and older with a diagnosis of dementia and 1 or more episodes of transient loss of consciousness of a suspected syncopal nature or unexplained falls during the previous 3 months. MEASUREMENTS: Blood pressure was measured in the supine position and in the orthostatic position after 1 and 3 minutes. OH was defined as a decrease in systolic blood pressure of 20 mmHg or more and in diastolic blood pressure of 10 mmHg or more within 3 minutes of standing. Univariate and multivariate analyses were used to evaluate associations between hypotensive drugs and their combinations with OH-related syncope. RESULTS: The mean age of the study population (n=522; women, n=324) was 83.5±6.1, and the most frequent comorbidity was arterial hypertension (74.5%); 324 (67.8%) participants had had a syncopal fall and 168 (32.2%) a nonsyncopal fall. The mean number of hypotensive drugs administered (2.9±3.1) did not differ between the two groups. Syncopal falls was OH-related in 170 participants (48.0%). OH-related syncopal falls were more frequent in participants receiving nitrates (15.3% vs 9.8%, p=.06), alpha-blockers (16.5% vs 9.8%, p=.04), or combinations of angiotensin-converting enzyme inhibitors (ACE-Is) and diuretics (20.6% vs 13.0%, p=.04), alpha-blockers and diuretics (8.2% vs 3.3%, p=0.036), and ACE-Is and nitrates (8.2% vs 3.3%, p=.10). Multivariate analysis confirmed a greater risk of OH-related syncopal fall for nitrates (relative risk (RR)=1.77), combinations of ACE-Is and diuretics (RR=1.66), and combinations of ACE-Is and nitrates (RR=2.32). CONCLUSION: In older adults with dementia, OH-related syncopal falls are significantly related to treatment with nitrates, combinations of ACE-Is and diuretics, and combinations of ACE-Is and nitrates.

In an effort to find new ocular hypotensive drug candidates, a total of 27 condensed benzimidazoles based compounds were screened. This study was done in normotensive rats and rebound tonometry was used to estimate IOP. All compounds were topically applied as a single drop, unilaterally, at 3 different concentrations (0.1%, 0.2% and 0.4%). The contralateral eye was instilled with vehicle and served as control. The IOP reduction was measured up to 6h. It was observed that with a single topical instillation, compounds RU 551, RU 555, RU839 (pyrimido[1,2-a]benzimidazole derivatives), and RU 615 (imidazo[1,2-a]benzimidazole derivative) showed significant IOP lowering activities in ocular normotensive rats. All other compounds showed none, weak and inconsistent IOP lowering effect. The relationship between ability of IOP lowering and hypotensive activities was studied. According to the pharmacophore analysis, the class of pyrimido[1,2-a]benzimidazole is more promising than the class of imidazo[1,2-a]benzimidazole as a source of compounds with high IOP lowering activity. Pharmacophore analysis also showed that the critical features of high IOP lowering activity are methoxyphenyl and [phenyl]alkyl fragments, and non-conjugated six-membered heterocyclic ring.

The review concerns amlodipine - the representative of the third generation of dihydropyridines. Amlodipine, being considered a hypotensive drug, has a broad spectrum of clinical effects beyond the hypotensive effects. It is shown that the drug has different pleiotropic effects, allowing using it as an anti-atherosclerotic and organoprotective funds. The data on the beneficial effect of amlodipine in pathology, is not included in the group of cardiovascular diseases - Raynaud's syndrome, migraine headaches, tendency to vomit.

This chapter describes methods of synthesis, pharmacological properties and the use of derivatives of piperidine-based fused biheterocycles represented on the pharmaceutical market as thienopyridine-derivatives such as ticlopidine, clopidogrel, and prasugrel—the primary platelet inhibitors, γ-carbolines such as antihistaminic mebhydrolin, atypical antipsychotics gevotroline and carvotroline, and hypotensive drug endralazine.

L’analyse phytochimique de l’extrait aqueux d’ecorce de racine de Zanthoxylum zanthoxyloides (FAZ) [Lam.] Waterman (Rutaceae) revele la presence de sterols et polyterpenes, de polyphenols, de flavonoides, de quinones ainsi que d’alcaloides. La richesse de cet extrait en composes phytochimiques est compatible avec les nombreux usages traditionnels de cette plante medicinale. L’etude toxicologique de FAZ a permis de determiner par la methode graphique de Miller et Tainter et par la methode par calcul de Dragsted et Lang respectivement une dose letale 50% (DL50) egale a 4168±462mg/kg de poids corporel (PC) et 5500±875mg/kg de PC. Ces valeurs indiquent que cet extrait aqueux d’origine naturelle n’est pas toxique. Aux doses comprises entre 2,7 × 10−4 et 5,5 × 10−1 g/kg de PC, cet extrait aqueux induit une hypotension soutenue, dose-dependante semblable a celle induite par l’acetylcholine (Ach) de 5,6 × 10−7 g/kg de PC a 5,5 × 10−4 g/kg de PC. Il reduit fortement l’hypertension induite par l’adrenaline (Adr) a 2,5 × 10−5 g/kg de PC. Ces resultats indiquent que l’extrait aqueux d’ecorce de Zanthoxylum zanthoxyloides est un hypotenseur. Ils justifient l’utilisation traditionnelle de cette plante pour traiter l’hypertension arterielle. L’inhibition partielle de l’effet hypotensif de FAZ par l’atropine, antagoniste competitif des recepteurs cholinergiques de type muscarinique, suggere la presence de deux types de principes actifs dans cet extrait aqueux: 1) les principes actifs cholinomimetiques de type muscarinique; 2) et les principes actifs non cholinomimetiques.

To compare responses in two patient populations with a questionnaire developed to identify those prescribed ocular hypotensive medication whose adherence may need improvement and who may be ready to change.The content/face validity of a 62-item, self-administered questionnaire was confirmed by nine glaucoma specialists. Questions concerned demographics, health and medications, use of/problems with medications, and visual function. The questionnaire was administered anonymously to 102 consecutive patients in a glaucoma referral practice ('glaucoma practice') and 100 from a multispecialty ophthalmology practice ('multispecialty practice'). All participants were prescribedor=1 ocular hypotensive medication and had no previous trabeculectomy.Patients in the glaucoma practice were more likely to be younger, African-American, and better educated (P0.05 for each). In both,80% had glaucoma with60% diagnosedor=3 years previously. Most (glaucoma, multispecialty: 87, 93%) reported administering drops every day, but more in the multispecialty practice reported administering drops at the same time every day (79, 92%; P0.05). Number of adherence problems (mean, 1/patient) and adherence scores (mean, 24; possible scale range, 0-25) were similar. Common adherence barriers were falling asleep and forgetting when the regular schedule changed or when travelling. In the glaucoma practice, the number of adherence problems was correlated with adherence score (r=-0.611; P0.0001) and number of side effects (r=0.349; P0.0001).Similarities between patient populations limited our ability to compare responses between groups or to propose adherence counselling tailored to specific demographics. Until such recommendations are possible, physicians should incorporate adherence counselling broadly into their practices.

Le present travail evalue le potentiel hypotensif et les mecanismes d’action associes de l’extrait semi-ethanolique de Biophytum petersianum chez le rat Wistar normotendu. La methode sanglante est utilisee pour mesurer la pression arterielle. L’extrait est administre par v.i. aux doses uniques de 27, 54 et 81 mg/kg. L’extrait a 54 mg/kg et la clonidine a 0,5 mg/kg sont administres a des animaux differents, suivie d’une bi-occlusion carotidienne. La meme dose d’extrait est administree apres bivagotomie et blocage des recepteurs muscariniques par l’atropine. Les resultats montrent que l’effet hypotenseur de l’extrait ne passe pas par l’inhibition du systeme nerveux sympathique mais implique partiellement la stimulation du systeme parasympathique puisque cet effet est bloque par l’atropine. Ces resultats confirment l’utilisation traditionnelle de B. petersianum dans le traitement de l’hypertension.

A series of 1-[3-(4-substituted phenylthio) propyl]-4-(substituted phenyl) piperazines has been synthesized and evaluated for hypotensive activity. The QSAR studies indicate that resonance and hydrophobic parameters of the aryl substituents are important for hypotensive activity. The similar role of resonance parameter in describing the variance of 5-HT 2A receptor binding affinities of these compounds suggests a possible role of 5-HT 2A receptors in mediating the hypotensive action of title compounds.

The leaf of Diospyros kaki is a traditional Chinese medicine, which has been used for treatment of stroke or syndrome and as a hypotensive drug. The pentacyclic triterpene acids, isolated from the leaves of Diospyros kaki, are their main bioactive compounds, which are very difficult and tedious to be obtained by conventional chromatography methods, especially for the separation of barbinervic acid and its epimer (rotungenic acid). In the present report, for the first time a one step preparative high speed countercurrent chromatography (HSCCC, with a 1000 mL coil column) method was developed for the separation and purification of four bioactive pentacyclic triterpene acids from this plant with a solvent system composed of n‐hexane–ethyl acetate–methanol–water (3:6:4:2, v/v/v/v). In a single operation, 49.6 mg of barbinervic acid (3α,19α,24‐trihydroxy‐urs‐12‐en‐28‐oic acid) and its epimer, 32.2 mg of rotungenic acid (3β,19α,24‐trihydroxy‐urs‐12‐en‐28‐oic acid) along with 11.0 mg of 24‐hydroxy ursol...

Background: We studied the effect of argon laser trabeculoplasty (ALT) on medically controlled, pressure-stable glaucoma patients to verify whether it is possible to reduce ocular hypotensive medication after ALT while keeping intraocular pressure levels similar to those observed before the procedure. Methods: Seventy-one consecutive chronic glaucoma patients, all of whom were taking ocular hypotensive medication and had intraocular pressure at adequate levels, underwent ALT. After the laser procedure, each patient discontinued one hypotensive drug. Mean follow-up was 16.39 ± 5.39 months. We performed diurnal pressure curves on each patient before and after trabeculoplasty to determine the effect on intraocular pressure. Results: In 39 (54.9%) patients, it was possible to reduce ocular hypotensive medication and still maintain intraocular pressure levels similar to those achieved before ALT. Interpretation: For some medically controlled, chronic glaucoma patients, ALT can reduce the amount of ocular hypotensive medication without significantly altering intraocular pressure.

The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2- b ]- and naphth[2,1- b ]-oxepin-5-ones ( 4 and 8 ) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100′ at a dose of 5 mg/kg iv in anaesthetized cats.

To study the effectiveness of monotherapy with bimatoprost in patients with decompensated intraocular pressure (IOP).90 patients (132 eyes) with stage I-II glaucoma and decompensated IOP previously treated with timolol, latanoprost and travoprost were included in the study. Average IOP at the beginning of the study was 25.4±2.5 mmHg. All patients had their hypotensive medications substituted by bimatoprost. The patients were examined during the initial appointment, as well as after 4 and 12 weeks.IOP decrease was highest in the group of patients who had been treated with timolol: initially IOP was 26.2±1.8 mmHg, after 4 weeks - 21.0±2.2 mmHg, after 12 weeks - 20.8±1.9 mmHg (p0.001). The initial IOP of patients who had been treated with latanoprost was 24.8±2.9 mmHg, 21.8±2.4 mmHg after 4 weeks, and 21.6±2.3 mmHg after 12 weeks (p0.001). Patients who had been treated with travoprost had 25.6±2.2 mmHg initially, 23.0±2.5 mmHg after 4 weeks, and 23.2±2.6 mmHg after 12 weeks (p0.001). By the end of the study IOP has decreased by 5.4, 3.2 and 2.4 mmHg in the groups of patients who had been treated with timolol, latanoprost and travoprost, respectively.Bimatoprost can be used as monotherapy if another hypotensive drug in monotherapy is insufficient for IOP compensation.Цель - изучить эффективность монотерапии биматопростом у пациентов с декомпенсированным внутриглазным давлением (ВГД). Материал и методы. В исследование включено 90 пациентов (132 глаза) с глаукомой I-II стадии и декомпенсированным ВГД, принимающих тимолол, латанопрост или травопрост. Средний уровень ВГД на момент начала исследования составлял 25,4±2,5 мм рт.ст. Всем больным заменяли инстиллируемый препарат на биматопрост. Пациентов наблюдали на первом визите, через 4 и 12 нед. Результаты. В группе пациентов, изначально принимавших тимолол, снижение уровня ВГД оказалось наиболее выраженным: перед началом лечения значения ВГД составляли 26,2±1,8 мм рт.ст., через 4 нед - 21,0±2,2 мм рт.ст., через 12 нед - 20,8±1,9 мм рт.ст (p0,001). У пациентов, принимавших латанопрост, начальный уровень ВГД составил 24,8±2,9 мм рт.ст., через 4 нед - 21,8±2,4 мм рт.ст., через 12 нед - 21,6±2,3 мм рт.ст (p0,001). В группе травопроста изначально показатели ВГД составляли 25,6±2,2 мм рт.ст., спустя 4 нед - 23,0±2,5 мм рт.ст., через 12 нед - 23,2±2,6 мм рт.ст. (p0,001). К концу исследования снижение уровня ВГД в группах пациентов, ранее принимавших тимолол, латанопрост и травопрост, составило 5,4; 3,2 и 2,4 мм рт.ст. соответственно. Заключение. Биматопрост может применяться в монотерапии при недостаточно эффективной монотерапии другим антиглаукомным препаратом.

The cardiovascular effects of i.v. treatment with 1,8-cineole, a monoterpenic oxide present in many plant essential oils, were investigated in normotensive rats. This study examined (i) whether the autonomic nervous system is involved in the mediation of 1,8-cineole-induced changes in mean aortic pressure (MAP) and heart rate (HR) and (ii) whether the hypotensive effects of 1,8-cineole could result from its vasodilatory effects directly upon vascular smooth muscle. In both pentobarbital-anesthetized and conscious, freely moving rats, bolus injections of 1,8-cineole (0.3–10 mg/kg, i.v.) elicited similar and dose-dependent decreases in MAP. Concomitantly, 1,8-cineole significantly decreased HR only at the highest dose (10 mg/kg). Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardic responses to 1,8-cineole (10 mg/kg) without affecting hypotension. In conscious rats, i.v. pretreatment with methylatropine (1 mg/kg), atenolol (1.5 mg/kg), or hexamethonium (30 mg/kg) had no significant effects on the 1,8-cineole-induced hypotension, while bradycardic responses to 1,8-cineole (10 mg/kg) were significantly reduced by methylatropine. In rat isolated thoracic aorta preparations, 1,8-cineole (0.006–2.6 mM) induced a concentration-dependent reduction of the contraction induced by potassium (60 mM). This is the first physiological evidence that i.v. treatment with 1,8-cineole in either anesthetized or conscious rats elicits hypotension; this effect seems related to an active vascular relaxation rather than withdrawal of sympathetic tone.Key words: 1,8-cineole, essential oil, cardiovascular effects, autonomic nervous system, isolated thoracic aorta.

The reaction of trans-[Ru(NH(3))(4)P(OEt)(3)NO](3+) and mitochondria was investigated through differential pulse polarography and fluorimetry. The nitrosyl complex undergoes one-electron reduction centered on the NO ligand site. The reaction between the mitochondrial reductor and trans-[Ru(NH(3))(4)P(OEt)(3)NO](3+) exhibits a second order specific rate constant calculated as k=2 x 10(1) M(-1) s(-1). The reduced species, trans-[Ru(NH(3))(4)P(OEt)(3)NO](2+), quickly releases NO, yielding trans-[Ru(NH(3))(4)P(OEt)(3)H(2)O](2+). The low toxicities of both trans-[Ru(NH(3))(4)P(OEt)(3)(NO)](2+) and trans-[Ru(NH(3))(4)P(OEt)(3)H(2)O](2+) and its ability to release NO after reductive activation in a biological medium make the nitrosyl compound a useful model of a hypotensive drug.

A sex-dependent protein from male rat liver was isolated. Male rats receiving reserpine for 15-20 weeks did not possess this protein in the liver. The growth of testes and seminal vesicles in experimental animals was also inhibited. Similar observations were made on male rats treated with catapresan, a hypotensive drug. The reserpine inhibition of sex-dependent protein biosynthesis and testicular weights could be reversed by a simultaneous treatment with mesterolone, an androgen without any antigonadotropic activity.

The effect of the constituents of the leaves of Persea americana on arterial blood pressure was investigated in anaesthetized normotensive rats. The intravenous administration induced a marked fall in mean arterial blood pressure which lasted 2–3 min. The short duration of action may be due to rapid metabolism.

TLC investigation of the flavonoid fraction of Chenopodium murale L. revealed the presence of three components. The major was identified as kaempferol-3,7-dirhamnoside 1 (kaempferitrin; lespedin) through its MP, UV, IR, MS and NMR (H-H COSY and H-C. HECTOR) spectra. Testing the effect of compound 1 as well as the total flavonoid mixture on the rabbit cardiovascular system, showed dose-related hypotension and bradycardia. Compound 1 also produced a dose-related hypotension in genetically prone hypertensive rats. Compound 1 did not block α1 or β1-adrenoceptors when tested using isolated guinea-pig aoric strip and atria, respectively. Quantification of 1 in C. ambrosoides, C. murale, C. ficifolium and C. album revealed that the former contains the highest level. © 1997 John Wiley & Sons, Ltd.

We have synthesized a number of novel bicyclic hexahydroaporphines containing a phenethylamine moiety for preliminary study as intraocular pressure lowering agents. The target molecules were synthesized in a twelve step process. The final products were secondary or tertiary amines containing either an aromatic methoxy or phenolic substituent. These molecules, in hydrochloride salt form, were assayed in doses ranging from 0.1-1.5%. All products and vehicle were administered topically to one eye of normotensive rabbits and intraocular pressure was measured in both eyes for up to six hours. Four of the five compounds examined produced a significant and, in some cases, prolonged, ocular hypotensive response. Secondary and N-methylated tertiary amines were equally effective, as were compounds containing either the 10-methoxy group of free phenol. Studies are currently in progress to optimize potency and identify functional and molecular mechanisms of action.

The purpose of this study was to compare the time course of the bradycardic and hypotensive effects of esmolol. Ten patients undergoing craniotomy requiring hypotension were anesthetized with nitrous oxide and isoflurane. During steady state anesthesia, the response to an infusion of esmolol 500 μg.kg -1 .min -1 for 90 s followed by 300 μg.kg -1 .min -1 was measured over 60 min. Heart rate (HR), mean arterial pressure (MAP), and plasma renin activity (PRA) responses did not occur with equal rapidity. The half-time for the 14% decrease in HR (81 ± 13 bpm to 70 ± 9 bpm) was 1.2 min. MAP decreased by 26% (85 ± 7 mm Hg to 63 ± 6 mm Hg) with a 17.8 min half-time. This delay in MAP response may, in part, be related to the gradual 44% decline in PRA (9.5 ± 4.5 ng.mL -1 .h -1 to 5.3 ± 2.5 ng mL -1 . h -1 ) occurring with a half-time of 11.9 min. The times to attainment of 90% maximum decreases were 4.8 ± 3.0 min for HR, 42.5 ± 8.9 min for MAP, and 32.1±15.0 min for PRA. Thus although esmolol has an ultrashort kinetic half-life, only the HR effect can be considered to have an ultrashort onset. (Anesth Analg 1995 ;81 :297-300)

Die vorliegende Untersuchung ging der Frage nach, ob eine kontrollierte Hypotension mit Nitroprussidnatrium (NPN) das Ausmas der Akutphasenreaktion beeinflust. Nach Genehmigung durch die Ethikkommission wurden 20 Patienten mit Nasen-Septumkorrektur-Operationen untersucht, von denen 10 eine kontrollierte Hypotension mit NPN erhielten. Die Narkose wurde mit Fentanyl, Etomidat eingeleitet und mit Isofluran in 66% N 2 0 und 33% O 2 fortgefuhrt. Die Interleukin-6-Plasmakonzentrationen (IL-6) stiegen in beiden Gruppen am 1. postoperativen Tag signifikant (p

The effects of chronic stress on the structure and function of the renal glomerular system were studied in hypertensive ISIAH rats treated with hypotensive drugs during the early ontogeny. The morphometric parameters of the renal glomerular system, characteristic of each of the experimental animal groups treated by enalapril, losartan, or terazosin in early age virtually did not change under conditions of stress exposure. These results indicate a persistent delayed nephroprotective effect of these drugs.

The radical cyclizations of (±)-(E)-3-((2-(bromomethyl)butoxy)carbonyl)- prop-2-enoates (11) and (12) and (±)-ethyl (E)-3-{N-[2-(bromomethyl)- butyl]-N-[2-(3-indolyl)ethyl]carbamoyl}prop-2-enoate (25) were carried out with (TMS) 3 SiH or Bu 3 SnH in the presence of AIBN. (-)-(2S)-2- ((tert-Butyldimethylsilyloxy)methyl)butan-1-ol (6), which was prepared by two different methods, was converted into (+)-25. The radical cycli- zation of(+)-25 produced piperidinone (18) as a diastereomeric mixture, which was transformed into tacamonine (1)

The hypotensive activities in rats of indolic compounds 1–9 were compared with that of reserpine. In spite of differences in their structure, all 9 showed similar hypotensive activities to that of reserpine. New octahydropyrazinopyridoindoles 3–6 and the tetrahydro-β-carboline 7 were synthesized.

A series of hydrazinopyridazine derivatives combined with a beta-blocking side chain were synthesized. When they were given intravenously to anesthetized rats, some of them exhibited both hypotensive and beta-blocking activities. Their structure-activity relationships for hypotensive and beta-blocking activities are discussed. Compound 11c had the best profile and was selected for further study.

Adrenalectomy for pheochromocytoma is reported with a mortality close to zero in recent studies. The dogma of preoperative fluid and hypotensive drug administrations is widely applied in patients scheduled for pheochromocytoma removal and is assumed to have a beneficial effect on operative outcomes. This paradigm is only based on historical studies of non-standardized practices and criteria for efficacy, with no control group. Pre- and intraoperative hypovolemia have never been demonstrated in patients scheduled for pheochromocytoma removal. Recent improvements in outcome of patients undergoing adrenalectomy for pheochromocytoma could also be the result of improvement in surgical techniques and refinement in anesthetic practices. Whether better knowledge of the disease, efficiency of available intravenous short-acting vasoactive drugs, and careful intraoperative handling of the tumor make it possible to omit preoperative preparation in most patients scheduled for pheochromocytoma removal is presently questionable. We reviewed available literature in this respect.

Mabrouka El Oudi1, Zied Aouni1, Haroun Ouertani2, Chakib Mazigh2, Salem Machghoul11Département de biochimie, 2Service d’endocrinologie, Hôpital militaire de Tunis, 1008 Montfleury, TunisieAim: Evaluate the effect of lipopenic and hypotensive treatment on homocysteine levels.Methods: We recruited 145 type 2 diabetics and 130 control subjects. Thirty-seven diabetics had no complications, 54 had microvascular complications and 54 had macrovascular complications. We determined the parameters homocysteine of lipid, vitamin B12, triglycerides, and folates for all subjects. Associated treatments used one or more of the following drugs, statin, fibrate, angiotensin-converting enzyme inhibitor and beta-blockers.Results: Hyperhomocysteinemia was present in 35.6% of patients. Diabetics had elevated serum levels of triglycerides (P < 0.001), homocysteine (P < 0.01), folates (P < 0.01) and vitamin B12 (P < 0.001). A strong association was found between type 2 diabetes and hyperhomocysteinemia (P < 0.001). Diabetics with associated treatment had elevated homocysteine, vitamin B12 and folate levels when compared to diabetes-free controls. For diabetics with macrovascular complications, we found significant differences in homocysteine (P = 0.010) and folate (P = 0.014) between those taking associated drugs and those who did not. For diabetics with microvascular complications, a significant difference was found in folate only (P = 0.012). Conclusion: Drugs used for hypertension and hyperlipidemia may have an effect on homocysteine levels, for this reason the interaction between drug action and homocysteine levels should be taken into consideration.Keywords: type 2 diabetes, complications, homocysteine, hypolipemiant drug, hypotensive drug