Potent Diuretic Research Articles

Functional Properties of Pentacyclic Triterpenes Contained in "Orujo" Olive Oil

Pomace oil (orujo olive oil), is an olive sub-product which possesses potential beneficial components (e.g. tetra- and pentacyclic triterpenes: oleanolic and maslinic acids, erythrodiol and uvaol) to which great variety of biological effects is attributed. Pharmacological properties of oleanolic acid have been demonstrated: anti-inflammatory, antitumoral, hepatoprotective, cytotoxic, anti-diabetogenic, antibacterial and anti-HIV activities. There is scarce evidence about the pharmacological effects of these triterpenoid on vascular events; the chronic treatment of Dahl salt-sensitive hypertensive rats with these natural compounds (oleanolic and ursolic acids) prevent the development of hypertension with significant bradycardia and potent diuretic activity. In relation to erythrodiol and uvaol, only their therapeutic efficiency on different experimental models of inflammation has been reported. Moreover, uvaol plays a protective role on the oxidation of lipoproteins of low density in vitro, as well as a protective effect on induced hepatic injuries. Maslinic acid is effective in the treatment of diseases caused by agents that use the serin-protease in their mechanism of infection, like the AIDS virus and it has capacity to prevent the damage caused by the free radicals. Therefore, the intake of orujo olive oil, as a source of these compounds, might be beneficial in this regard.

Diuretic Activity of Cocos nucifera Husk in Rats

Objective: Husk of Cocos nucifera was screened for diuretic properties. Method: The diuretic properties of aqueous and alcoholic extract of Cocos nucifera husk were evaluated by determination of urine volume, electrolyte concentration and diuretic potency in male albino rats. Different concentrations of aqueous and alcoholic extract (250 mg/kg, 500mg/kg) were orally administered to hydrated rats and their urine output was immediately measured after 5 h of treatment. Frusemide (10mg/kg) was used as reference drug while normal saline (0.9%) solution was used as control. Result: Both the extract exhibited dose dependent diuretic property. The onset of diuretic action was extremely prompt (within 1 h) and lasted throughout the studied period (upto 5 h). Both extract caused marked increase in Na + , K + and Cl - level. Conclusion: The result of this experiment suggests that Cocos nucifera husk extract possessed significant diuretic activity.

Part 7.4: Monitoring and Medications

This section provides an overview of monitoring techniques and medications that may be useful during CPR and in the immediate prearrest and postarrest settings. ### Assessment During CPR At present there are no reliable clinical criteria that clinicians can use to assess the efficacy of CPR. Although end-tidal CO2 serves as an indicator of cardiac output produced by chest compressions and may indicate return of spontaneous circulation (ROSC),1,2 there is little other technology available to provide real-time feedback on the effectiveness of CPR. ### Assessment of Hemodynamics #### Coronary Perfusion Pressure Coronary perfusion pressure (CPP = aortic relaxation [diastolic] pressure minus right atrial relaxation phase blood pressure) during CPR correlates with both myocardial blood flow and ROSC (LOE 3).3,4 A CPP of ≥15 mm Hg is predictive of ROSC. Increased CPP correlates with improved 24-hour survival rates in animal studies (LOE 6)5 and is associated with improved myocardial blood flow and ROSC in animal studies of epinephrine, vasopressin, and angiotensin II (LOE 6).5–7 When intra-arterial monitoring is in place during the resuscitative effort (eg, in an intensive care setting), the clinician should try to maximize arterial diastolic pressures to achieve an optimal CPP. Assuming a right atrial diastolic pressure of 10 mm Hg means that the aortic diastolic pressure should ideally be at least 30 mm Hg to maintain a CPP of ≥20 mm Hg during CPR. Unfortunately such monitoring is rarely available outside the intensive care environment. #### Pulses Clinicians frequently try to palpate arterial pulses during chest compressions to assess the effectiveness of compressions. No studies have shown the validity or clinical utility of checking pulses during ongoing CPR. Because there are no valves in the inferior vena cava, retrograde blood flow into the venous system may produce femoral vein pulsations.8 Thus palpation of a pulse in the femoral triangle may indicate venous rather than arterial …

A multispecies study to assess the toxic and genotoxic effect of pharmaceuticals: Furosemide and its photoproduct

Pharmaceutical products for humans and animals, as well as their related metabolites end up in the aquatic environment after use. Recent investigations show that concentrations of pharmaceuticals are detectable in the order of ng/l–μg/l in municipal wastewater, groundwater and also drinking water. Little is known about the effects, and the hazard of long-term exposure to low concentrations of pharmaceuticals for non-target aquatic organisms. This study was designed to assess the ecotoxicity of furosemide, a potent diuretic agent, and its photoproduct in the aquatic environment. Bioassays were performed on bacteria, algae, rotifers and microcrustaceans to assess acute and chronic toxicity, while the SOS Chromotest and the Ames test were utilized to detect the genotoxic potential of the investigated compounds. A first approach to risk characterization was to calculate the environmental impact of furosemide by measured environmental concentration and predicted no effect concentration ratio (MEC/PNEC). To do so we used occurrence data reported in the literature and our toxicity results. The results showed that acute toxicity was in the order of mg/l for the crustaceans and absent for bacteria and rotifers. Chronic exposure to these compounds caused inhibition of growth population on the consumers, while the algae did not seem to be affected. A mutagenic potential was found for the photoproduct compared to the parental compound suggesting that byproducts ought to be considered in the environmental assessment of drugs. The risk calculated for furosemide suggested its harmlessness on the aquatic compartment.

Combination Therapy with Metolazone and Loop Diuretics in Outpatients with Refractory Heart Failure: An Observational Study and Review of the Literature

Metolazone is a potent thiazide-like diuretic. It is recommended in severe congestive heart failure (HF). We conducted a review of the existing literature and found that the available information on the use of metolazone in HF is based on studies containing less than 250 patients in total. Nevertheless, metolazone is widely used, often in combination with a loop diuretic. Absorption of metolazone seems to be reduced in HF. Metolazone produces a diuretic response despite a low glomerular filtration rate. A wide dose range of metolazone has been investigated (< or =2.5 to 200 mg), leaving no clear dosing recommendation. However, in most studies a low starting dose (< or =5 mg) was used. We further report an observational study on 21 patients with refractory systolic HF from our specialized outpatient HF clinic. The aim was to evaluate the effects of metolazone in combination with a loop diuretic in contemporary HF patients. We registered 42 episodes of treatment with metolazone. The maximal dose of metolazone was 5 mg. NYHA functional class improved. A significant reduction during treatment in weight, blood pressure, plasma-sodium and -potassium was seen whereas plasma-BUN and -creatinine increased significantly. Clinically important hypokalemia (<2.5 mM) or hyponatremia (<125 mM) were observed during 10% of the treatment episodes. The literature review and the observational study support the use of low-dose metolazone (< or =5 mg) on top of oral loop diuretics, as an effective and relatively safe treatment in contemporary outpatients with refractory HF.

Pharmacology Review

After completing this article, readers should be able to: 1. Review the actions of the diuretic agents commonly used in neonates. 2. Delineate the adverse effects of diuretic therapy. 3. Determine the roles of diuretics in therapy. Diuretics represent one of the most common classes of drugs administered to sick neonates and infants. Unwanted fluid retention arising from myriad neonatal disorders can and does complicate the optimal care of sick infants. To appreciate the many factors that influence a patient’s response to diuretic therapy and clinical and laboratory monitoring, we direct readers to the article “The Ontogeny of Human Kidney Development: Influence on Neonatal Diuretic Therapy” in this issue. All the clinically relevant diuretics, with the exception of aldosterone receptor antagonists (eg, spironolactone), must achieve sufficient free drug concentrations within the renal tubular lumen to reach their sites of action. Thus, diuretic effectiveness ultimately is guided by the functional capacity of the kidney, which clearly is influenced by infants’ gestational and postnatal ages. This article addresses the most common diuretics used in the neonate and young infant, focusing on the pharmacokinetic and pharmacodynamic characteristics of each drug relative to the infant’s postconceptional age and other factors that influence the infant’s overall response to therapy. ### “Loop” or “High Ceiling” Diuretics All diuretics, with the exception of spironolactone, must reach the renal tubular lumen to exert their pharmacologic effect. A lower renal blood flow (RBF) in preterm infants reduces the amount of drug delivered to the kidney, potentially limiting diuretic effectiveness. Highly protein-bound, loop diuretics (Table 1) are filtered minimally at the glomerulus. Instead, these agents are carried to the proximal tubule where they are actively secreted into the lumen via the organic acid transport pump. Luminal flow then carries the loop diuretics to their sites of action. | Loop Diuretics | || | •Bumetanide | | •Furosemide | | •Torsemide | | Thiazide Diuretics | | •Chlorothiazide | | •Chlorthalidone | | •Hydrochlorothiazide | | •Indapamide | | •Metolazone | | Aldosterone Antagonists | | •Eplerenone | | •Spironolactone | Table 1. Commonly Used Diuretic Drugs in Preterm and Newborn Infants Loop diuretics bind …

Clinical Relevance of Biological Variation of B-Type Natriuretic Peptide

The cardiac natriuretic hormones (CNHs), atrial (ANP) and B-type natriuretic peptide (BNP), are peptides produced and secreted by the atrial and ventricular cardiomyocytes, respectively. ANP and BNP share potent diuretic, natriuretic, and vascular smooth-muscle-relaxing effects and interact with the hormonal and nervous systems (1)(2)(3). Stimulation by hemodynamic overload, as well as by several neuroendocrine (including α-adrenergic agonists, angiotensin II, endothelins, and vasopressin) and immunologic agents and by growth factors, modulates the production of CNHs by the human heart (1)(2). CNHs and their respective counter-regulatory neurohormonal systems (including the adrenergic, endothelin, and renin-angiotensin-aldosterone systems) form a physiologic negative feedback mechanism that regulates cardiac output by controlling blood pressure and heart rate as well as by fluid and electrolyte homeostasis (1)(2). The clinical relevance of measurement of BNP and its related peptides as diagnostic tools and prognostic markers in patients with cardiovascular diseases has been confirmed recently (2)(3). To achieve correct interpretation of serial test results that are collected for follow-up or for tailored treatment of heart …

Atrial natriuretic peptide release associated with smoke inhalation and physiological responses to thermal injury in sheep

Markedly elevated levels of plasma atrial natriuretic peptide (ANP), which exhibit potent diuretic and vasoactive properties, has been well documented in patients with acute lung injury. We examined the physiological effects of additional smoke inhalation on plasma ANP concentrations in an ovine burn model. Seventeen sheep were instrumented to receive fluid and have physiological measurements taken. The burn group ( n = 8) received 40% body surface area third degree burn and the burn + smoke group ( n = 9) received the same burn plus 48 breaths of cotton smoke insufflation. The animals were resuscitated according to the Parkland formula with Ringer's lactate in the following 72 h period. Hemodynamic, oxygenation, fluid balance, and plasma ANP levels were serially determined. The effects of smoke inhalation manifested as deteriorated oxygenation, and increased fluid accumulation after a sustained initial shock period of more than 12 h. Plasma ANP levels in the burn + smoke group showed a biphasic elevation, whereas the burn group showed no appreciable changes throughout the whole experimental period. The initial increase in plasma ANP concentrations occurred immediately after injury (from 96 ± 10 at baseline to 136 ± 17 pg/mL at 3 h after injury); thereafter, it decreased towards baseline value, followed by a second increase in the post resuscitation period (183 ± 43 pg/mL at 72 h after injury). Decreased urine output and accentuated pulmonary vascular resistance in the combined injury group was observed between the two ANP level peaks, indicating that ANP release modified physiological responses to the burn + smoke injury

The bioavailability of furosemide-polyethylene glycol (PEG 4000) solid dispersion in male rabbits

Furosemide is a potential diuretic drug usually used for the secondary treatment of hypertension. Unfortunately this agent is very slightly soluble in water, so it has poor bioavailability. The oral administration of drug shows that only 60 % of the dose can be absorbed. The aim of the present study is to increase the bioavailability of furosemide by mixing the furosemide-PEG 4000 solid dispersion (1 : 1) in capsule dosage forms (formula A). The powder of LasixR tablet in capsules was used as a standard reference (formula B), and the original powder of furosemide in capsules was used as control (formula C). All of the formulas contained 40 mg of furosemide. The bioavailability of these formulas was evaluated following oral administration in male rabbits using The Latin Square Cross Over Design, then the plasma furosemide concentrations were analyzed spectrofluorometrically. The results indicated that the bioavailability of furosemide in the formula A was equal to that of the formula B (P > 0,05) or both formulas were bioequivalent. But the Cpmax value of the formula C was significantly lower in comparison with the formulas A and B. Key words: furosemide, solid dispersion, bioavailability.

Bremazocine: A κ‐Opioid Agonist with Potent Analgesic and Other Pharmacologic Properties

Bremazocine is a kappa-opioid receptor agonist with potent analgesic and diuretic activities. As an analgesic it is three- to four-times more potent than morphine, as determined in both hot plate and tail flick tests. Bremazocine and other benzomorphan analogs were synthesized in an effort to produce opiates with greater kappa-opioid receptor selectivity and with minimal morphine-like side effects. Unlike morphine bremazocine is devoid of physical and psychological dependence liability in animal models and produces little or no respiratory depression. While bremazocine does not produce the characteristic euphoria associated with morphine and its abuse, it has been shown to induce dysphoria, a property that limits its clinical usefulness. Similarly to morphine, repeated administration of bremazocine leads to tolerance to its analgesic effect. It has been demonstrated that the marked diuretic effect of bremazocine is mediated primarily by the central nervous system. Because of its psychotomimetic side effects (disturbance in the perception of space and time, abnormal visual experience, disturbance in body image perception, de-personalization, de-realization and loss of self control) bremazocine has limited potential as a clinical analgesic. However, its possible utility for the therapy of alcohol and drug addiction warrants further consideration because of its ability to decrease ethanol and cocaine self-administration in non-human primates. In addition, the ability of bremazocine-like drugs to lower intraocular pressure and to minimize ischemic damage in animal models suggests their possible use in the therapy of glaucoma and cardiovascular disease.

Endocrine Paradox in Heart Failure: Resistance to Biological Effects of Cardiac Natriuretic Hormones

We read the interesting minireview by Goetze (1) concerning the biochemistry of pro-B-type natriuretic peptide (proBNP)-derived peptides: the main message is the potential clinical relevance of the proBNP-derived peptides, which should be considered for current clinical interpretation of plasma BNP concentrations and be the focus of ongoing research. Accordingly, the lack of accurate studies on in vivo production/secretion mechanisms and metabolism of BNP- and proBNP-related peptides explains the incomplete knowledge of the pathophysiologic significance of this hormone system. Thus, we agree with Goetze that deeper insight into the biochemistry of these peptides could pave the way for more sensitive and disease-specific assays in the clinical setting. We have some observations concerning the presence of an “endocrine paradox in heart failure” (1). The lack of encoding and processing of the precursor peptides to the mature hormones, atrial natriuretic peptide (ANP) and BNP, which have a potent diuretic and natriuretic effect, could explain the disturbed electrolyte and fluid homeostasis occurring in chronic heart failure (2)(3). However, the hypothesis of heart failure as a syndrome of cardiac natriuretic hormone (CNH) deficiency was challenged when this system was investigated in experimental animals and in humans. In fact, patients with congestive heart failure [New York Heart Association (NYHA) classes III–IV] have greatly increased plasma concentrations of CNHs compared with healthy individuals (up to 500-fold or more for plasma BNP concentration) (1)(2)(3). Goetze (1) tries to explain this paradox of heart failure (i.e., highly increased CNH concentrations in patients with sodium retention) by suggesting that a part of circulating CNH-related peptides (especially proBNP-related peptides) is not biologically active. We agree that increased concentrations of immunoreactive, but biologically inactive, proBNP-related peptides (as well as proANP-related peptides) are present in patients with heart failure. As also correctly pointed out in the … [↵][1]aAddress correspondence to this author at: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. Fax 45-35454640; e-mail jpg{at}dadlnet.dk. [1]: #xref-corresp-2-1

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.

Pass the Salt

Sodium is the most abundant extracellular ion. Historically, therapy with hypertonic saline was widely used for a variety of conditions. Currently, there are 3 primary indications for its use in critical care: hyponatremia, volume resuscitation, and brain injury. SIADH and CSW syndrome may require sodium replacement, but most cases of hyponatremia can be managed without administration of hypertonic saline. Studies of use of hypertonic saline in hypovolemia and brain injury are promising, but additional research is needed to better define optimal dosing regimens and to determine the relative risks associated with hypertonic saline versus conventional treatment for the management of patients with head injuries and for volume resuscitation in shock states.

An active insect kinin analog with 4-aminopyroglutamate, a novel cis-peptide bond, type VI beta-turn motif.

The insect kinins are potent diuretic peptides that preferentially form a cis-Pro, type VI beta-turn. An insect kinin analog containing (2S,4S)-4-aminopyroglutamate, a novel cis-peptide bond, type VI beta-turn motif, demonstrates significant activity in the physiological range in a cricket diuretic assay. This is the first instance of a 4-aminopyroglutamate analog of a peptide with a preference for a type VI turn that demonstrates significant bioactivity. The results provide further confirmatory evidence for the active conformation of the insect kinins, and a new scaffold with which to design biostable, peptidomimetic analogs capable of disrupting critical insect kinin-regulated processes in insects.

EPR study of free radicals in γ-irradiated thiazide compounds

The aim of this paper was to identify the type of radicals formed by γ-irradiation in powdered chlorothiazide (CTZ), hydrochlorothiazide (HCTZ), althiazide (ATZ) and trichloromethiazide (TCTZ) on the basis of analysis of their electron paramagnetic resonance spectra with enhanced resolution. In TCTZ, HCTZ and ATZ the radical was formed by abstraction of a hydrogen atom from the carbon atom C-3, and in the case of CTZ by addition of a hydrogen atom to the nitrogen atom N-4. The hyperfine structure is found. The electron densities at nitrogen atom positions in the N-C-N group in HCTZ, ATZ and TCTZ depend on a single 3-position substitution and are in line with their diuretic potency.

Potent cardiorenal actions in experimental heart failure with dual activation of soluble and particulate guanylate cyclases by bay 58-2667 and B-type natriuretic peptide: a novel therapeutic strategy

Background: Soluble guanylate cyclase (sGC) is an important enzyme, which via cyclic guanosine monophosphate (cGMP) production mediates potent vasodilating actions in multiple vascular beds. Particulate guanylate cyclase (pGC) via cGMP results in potent renal natriuretic and diuretic actions with vasodilating properties. Importantly, sGC and pGC may in part be differentially localized which may limit maximal cGMP activating pathways with sole activation of either pGC or sGC. BAY 58-2667 belongs to the new pharmacological class of direct sGC activators that, unlike conventional nitrates, activate sGC without the development of tolerance and without cGMP-independent actions. B-type natriuretic peptide (BNP), which is a pGC activator, is natriuretic and vasodilating, but in experimental congestive heart failure (CHF) does not increase cardiac output or reduce systemic vascular resistance. We hypothesized that co-administration of BAY 58-2667 and BNP in experimental CHF would complement the beneficial cardiac unloading actions of BAY 58-2667 with the beneficial renal actions of BNP. Methods: CHF was induced in two groups of male dogs (both N=7) by tachypacing. After 10 days, cardiorenal parameters were measured in clearances at baseline and with two intravenous doses of BAY 58-2667 (0.1 and 0.3 μg/kg/min, respectively) alone or in combination with BNP (10 and 50 ng/kg/min, respectively). Clearances were compared within groups by repeated measures ANOVA, while groups were compared qualitatively. Results: BAY 58-2667 alone potently (p<0.05) decreased mean arterial pressure, cardiac filling pressures, and systemic and renal vascular resistance, while cardiac output and renal blood flood increased. These actions occurred to a similar degree when BNP was added to BAY 58-2667. However, in addition there were significant (p<0.05) increases in urinary flow, urinary sodium excretion, glomerular filtration rate, and filtration fraction. Both regimens did not further activate the renin-angiotensin-aldosterone system. Conclusion: Direct sGC activation by BAY 58-2667 has potent beneficial cardiac unloading actions in experimental CHF. While additional pGC activation with BNP does not augment hemodynamic actions with BAY 58-2667, it enhances renal function. These findings suggest that coactivation of sGC and pGC may be a beneficial and a novel strategy in the treatment of CHF.

Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release.

Apelin, a recently isolated neuropeptide that is expressed in the supraoptic and the paraventricular nuclei, acts on specific receptors located on vasopressinergic neurons. The increased phasic pattern of these neurons facilitates sustained antidiuresis during dehydration or lactation. Here, we investigated whether apelin interacts with arginine vasopressin (AVP) to maintain body fluid homeostasis. We first characterized the predominant molecular forms of endogenous hypothalamic and plasma apelin as corresponding to apelin 13 and, to a lesser extent, to apelin 17. We then demonstrated that, in lactating rats, apelin was colocalized with AVP in supraoptic nucleus magnocellular neurons and given intracerebroventricularly inhibited the phasic electrical activity of AVP neurons. In lactating mice, intracerebroventricular administration of apelin 17 reduced plasma AVP levels and increased diuresis. Moreover, water deprivation, which increases systemic AVP release and causes depletion of hypothalamic AVP stores, decreased plasma apelin concentrations and induced hypothalamic accumulation of the peptide, indicating that AVP and apelin are conversely regulated to facilitate systemic AVP release and suppress diuresis. Opposite effects of AVP and apelin are likely to occur at the hypothalamic level through autocrine modulation of the phasic electrical activity of AVP neurons. Altogether, these data demonstrate that apelin acts as a potent diuretic neuropeptide counteracting AVP actions through inhibition of AVP neuron activity and AVP release. The coexistence of apelin and AVP in magnocellular neurons, their opposite biological effects, and regulation are likely to play a key role for maintaining body fluid homeostasis.

Modulation of Sodium Pumps by Steroidal Saponins

Costus spicatus, used in Brazilian traditional medicine to expel kidney stones, contains steroidal saponins with different chemical characteristics. In spite of its popular utilization as potent diuretic, no scientific reports correlate this activity with the chemical constituents of the extract. Therefore, two steroidal saponins (3 beta,22 alpha,25R)-26-(beta-D-glucopyranosyloxy)-2-methoxyfurost-5-en-3-yl O-D-apio-beta-D-furanosyl-(1-->2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-->4)]-beta-D-glucopyranoside (1) and (3 beta,22 alpha,25R)-spirostan-3-yl O-D-apio-beta-D-furanosyl-(1-->2)-O-[6-deoxy-alpha-L-mannopyranosyl-(1-->4)]-beta-D-glucopyranoside (1a), were isolated from the rhizomes of this plant and their effects on the Na+-ATPase and (Na+ + K+)-ATPase activities of the proximal tubule from pig kidney were evaluated. It was observed that 1 and 1a inhibit specifically the Na+-ATPase activity.

Preliminary Phytochemical Investigation and Diuretic Studies of Alstonia boonei Stem Bark in Male Wistar Rats

Objective: Stem bark of Alstonia boonei was screened phytochemically for the presence of various plant secondary metabolites and for diuretic properties. Methods: The diuretic properties of 3 extracts of A. boonei stem bark were evaluated by determination of urine volume, electrolyte concentration and diuretic potency in male Wistar rats. Extracts were administered orally at doses of 250 and 500mg/kg respectively. In the assay frusemide, was used as reference drug while 0.9% saline was used as control. Results: Preliminary phytochemical examination of this drug indicated the presence of indole alkaloids and saponins but absence of anthraquinones and cardenolides. All the extracts exhibited a dose dependent diuretic property with the methanol extract displaying the highest activity with a potency value of 2.0 at a dose of 500mg/kg/hour while the same dose of hexane and chloroform gave a value of 1.9 and 1.0 respectively. Conclusion: The result of this experiment suggest that Alstonia boonei stem bark extract possessed significant diuretic activity and may be useful in the treatment of urinary oedema and hypertension.

Conivaptan: YM 087.

Conivaptan [YM 087], a benzazepine derivative, belongs to a series of highly potent, orally active arginine vasopressin V1 and V2 receptor antagonists that are being developed by Yamanouchi. Yamanouchi licensed conivaptan to Warner-Lambert for co-development and marketing in the Americas, Europe and Africa. In return, Yamanouchi has rights to market atorvastatin in Japan. In June 2000, Warner-Lambert merged with Pfizer. The resulting company retained the Pfizer name. However, Yamanouchi and Pfizer discontinued the co-development and marketing agreement for conivaptan. Yamanouchi is continuing the independent development of conivaptan in the US and Europe. Yamanouchi is developing an oral drug delivery formulation of conivaptan for administration in patients with chronic heart failure. The company has initiated the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial, a double-blind, multicentre trial in which 345 patients with heart failure will receive placebo or one of three doses of conivaptan for 12 weeks and their functional capacity will be assessed. Conivaptan demonstrated a potent diuretic effect in animal studies.