Diuretic Effect In Rats Research Articles

Formulation and Evaluation of Diuretic Activity of Polyherbal Drug in Rats

An attempt was made in this study to investigate the diuretic activity of an ethanolic extract of a polyherbal formulation containing four drugs: seeds of Coriandrum sativum, buds of Syzigiumaromaticum, leaves of Ocimum sanctum, and curcumin (Curcuma longa), as well as leaves of Syzigiumaromaticum. According to the findings of this investigation, the extract of a polyherbal formulation (including seeds of Coriandrum sativum, buds and leaves of Syzigiumaromaticum& leaves of Ocimum sanctum, and Curcuma longa) possessed substantial activity. Various quantities of Polyherbal formulations (200 and 400 mg/kg), furosemide (10 mg/kg), and vehicle were given orally to rats (n = 6 animals per group), and the urine output was collected after 24 hours. All concentrations of Polyherbal formulation exhibited a dose-dependent relationship when compared to the control animals in the study. According to the findings of this study, the Polyherbal formulations have significant diuretic effect in rats when tested in the above-mentioned experimental model. That polyherbal formulation extract has such potent effect may be due to their ability to stimulate the excretion of Na+, K+, and Cl- concentrations in urine while also increasing the amount of urine excreted by the body. As diuretics, medicinal herbs are a key source of supply. When it comes to diuretics, both mono- and poly-herbal formulations have been employed successfully

A rare 6-O-glucoside flavonoid from Citharexylum myrianthum Cham. exhibit diuretic and potassium-sparing effect in rats

Citharexylum myrianthum Cham. belongs to the Verbenaceae family, which is widespread in traditional medicine and has promising therapeutic potential. However, studies about C. myrianthum are rare in the literature. Therefore, this study shows the isolation and identification of the main chemical constituents present in this plant species and its diuretic effect in rats. A glucoside flavonoid (1), 6-O-glycosyl-4′,5-dihydroxy-3′,7-dimethoxyflavone, was isolated from hexane fraction of leaves by precipitation, and its aglycone (2), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, was obtained by acid hydrolysis. Their structures were characterized by spectroscopic analysis, including 1D and 2D NMR, LC-ESI-MS/MS, and EIMS data in comparison with literature. Compound 1 is a rare example of natural products, featured as a flavonoid with an O-glucoside moiety on the C-6 position. Both compounds 1 and 2 showed a diuretic and natriuretic effect at a dose of 3 mg/kg. Besides, compound 1 revealed a potassium-sparing effect. Atropine (a non-selective muscarinic receptor antagonist) and indomethacin (a cyclooxygenase inhibitor) fully prevented compound 1 and 2-induced diuresis. For the first time, our study demonstrates the diuretic effect of the flavonoid 1 and its aglycone 2 in rats.

Development of polyherbal formulation and evaluation of its diuretic activity in rats

An attempt was made in this study to investigate the diuretic activity of an ethanolic extract of a polyherbal formulation containing four drugs: seeds of Coriandrum sativum, buds of Syzigium aromaticum, leaves of Ocimum sanctum, and curcumin (Curcuma longa), as well as leaves of Syzigium aromaticum. According to the findings of this investigation, the extract of a polyherbal formulation (including seeds of Coriandrum sativum, buds and leaves of Syzigium aromaticum & leaves of Ocimum sanctum, and Curcuma longa) possessed substantial activity. Various quantities of Polyherbal formulations (200 and 400 mg/kg), furosemide (10 mg/kg), and vehicle were given orally to rats (n = 6 animals per group), and the urine output was collected after 24 hours. All concentrations of Polyherbal formulation exhibited a dose-dependent relationship when compared to the control animals in the study. According to the findings of this study, the Polyherbal formulations have significant diuretic effect in rats when tested in the above-mentioned experimental model. That polyherbal formulation extract has such potent effect may be due to their ability to stimulate the excretion of Na+, K+, and Cl- concentrations in urine while also increasing the amount of urine excreted by the body. As diuretics, medicinal herbs are a key source of supply. When it comes to diuretics, both mono- and poly-herbal formulations have been employed successfully.

Diuretic, Natriuretic and Ca2+-Sparing Effects Induced by Rosmarinic and Caffeic Acids in Rats

This study aimed to investigate the possible diuretic effect in rats of two widely distributed bioactive compounds, rosmarinic and caffeic acids, derived from plants used in popular medicine, as well as to demonstrate their effects against in vitro calcium oxalate crystallization. Male Wistar rats were orally treated with vehicle, hydrochlorothiazide, rosmarinic acid, or caffeic acid. The volume and the urinary parameters were evaluated at the end of 8 h. The antiurolithiatic effect of the compounds was verified in vitro. Treatment with rosmarinic acid (3 mg/kg) or caffeic acid (10 mg/kg) significantly increased urine volume when compared with vehicle-treated rats, an effect associated with augmented urinary Na+ excretion. Interestingly, while rosmarinic acid showed a K+-sparing effect, caffeic acid significantly increased urinary K+ excretion, similarly to the group treated with hydrochlorothiazide (10 mg/kg). The two compounds showed a Ca2+-sparing effect. Therefore, the in vitro analysis of urinary calculi revealed that rosmarinic acid and caffeic acid, in concentrations ranging from 0.03 to 0.3 mg/ml, reduced the number of monohydrate and dihydrate forms of calcium oxalate crystals formed in the urine, suggesting a potential antiurolithiatic effect of these compounds.

Hypotensive, vaso-relaxant, cardio-depressant and diuretic effect of crude extract of <i>Crotalaria burhia</i> (Fabaceae)

Purpose: To examine 70 % aqueous-methanol crude extract of Crotalaria burhia (Cb.Cr) for its hypotensive and diuretic effects.
 Methods: The effect of intravenous administration of Cb.Cr on blood pressure (BP) of normotensive anesthetized rats was studied. In vitro experiments on rabbit isolated aortic and atrial preparations were performed to elucidate the mechanism of action. The diuretic effect was assessed following oral administration of Cb.Cr in rats.
 Results: Intravenous administration of Cb.Cr produced 14.70 ± 1.21, 22.00 ± 2.24 and 36.21 ± 2.65 % reduction in mean arterial blood pressure of the rats at doses of 1, 3 and 10 mg/kg, respectively. It was more potent in relaxing potassium (80 mM)- than phenylephrine (1 μM)-induced contractions in isolated aorta of rabbit with half-maximal effective concentration (EC50) values of 0.58 ± 0.03 and 1.58 ± 0.16 mg/mL, respectively, which are similar to verapamil. The extract showed depressant effects on spontaneously beating atrial preparations of rabbit in a dose-dependent manner. Moreover, Cb.Cr also increased urine volume and urinary electrolyte excretion in rats.
 Conclusion: Crotalaria burhia crude extract exhibits hypotensive and diuretic effects in rats. The hypotensive activity of the extract possibly involves vasodilator, cardio-depressant, calcium channel blocking and diuretic actions.
 Keywords: Khip, Crotalaria burhia, Calcium channel blocker, Antihypertensive, Diuretic

In Vivo Diuretic Activity of Hydromethanolic Extract and Solvent Fractions of the Root Bark of Clerodendrum myricoides Hochst. (Lamiaceae)

Introduction Clerodendrum myricoides (Lamiaceae) has been traditionally used for the treatment of various ailments, including body swelling and urine retention. The present study aimed to evaluate the diuretic activity of a crude extract and solvent fractions of the root bark of C. myricoides. Methodology. The coarsely powdered root bark of C. myricoides was extracted by a cold maceration method using 80% methanol. A portion of the extract was fractionated based on the polarity index of solvents to obtain chloroform, ethyl acetate, and aqueous fractions. To investigate the diuretic activity of the plant, rats were divided into fifteen groups. The normal control groups received either water or 2% tween 80, the standard group received furosemide (10 mg/kg), and the test groups were administered the hydromethanolic extract and solvent fractions at the doses of 100, 200, and 400 mg/kg by the oral route. The urine volume, urine pH, urine, and serum electrolytes were determined and compared with the standard and normal control groups. Results The crude hydromethanolic extract, ethyl acetate, and chloroform fractions induced significant diuresis at a dose of 400 mg/kg (P < 0.001) compared to the aqueous fraction. The hydromethanolic extract at 200 mg/kg and 400 mg/kg also caused noticeable diuresis (P < 0.001) compared to the standard, furosemide. Rats treated with hydromethanolic extract, ethyl acetate, and chloroform fractions showed delayed onset and prolonged diuresis in a dose-dependent fashion compared to the aqueous fraction (P < 0.05). The hydromethanolic extract and solvent fractions produced the highest saliuretic and natriuretic index compared to the standard, furosemide. The crude hydromethanolic extract also failed to produce any sign of toxicity up to 2000 mg/kg. Conclusion From this study, the hydromethanolic extract and ethyl acetate fraction of the root bark of C. myricoides produced a prominent diuretic effect in rats.

Effects of ethanol extract from Bidens pilosa L. on spontaneous activity, learning and memory in aged rats.

Bidens pilosa L., a herbal medicine, is rich in flavonoids, but its anti-aging effect on neurocognitive functions is not well understood. In the present study, we investigated the effects of ethanol extract from Bidens pilosa L. (EEBP) on spontaneous activity, learning and memory in aged rats. Forty aged (21.90 ± 0.22 months) and 10 young (10 weeks) adult male Sprague-Dawley rats were divided into 5 groups, which were respectively treated orally with 0 mg/kg (young and aged control), 25 mg/kg, 50 mg/kg and 100 mg/kg of EEBP for 30 days consecutively. Then, the animals were examined with open-field, passive avoidance and Morris water maze tasks. In the open-field task, compared with the aged control, the EEBP animals exhibited more rearing (50 mg/kg, P < 0.01) and urination (50 mg/kg, P < 0.01), but less defecation (P < 0.05). In the passive avoidance task, the retention latencies were longer than those in the training phase in all other groups (P < 0.01) except the aged control (P > 0.05). Compared with the young control, the retention latency of the aged control decreased (P < 0.01), but that of the EEBP animals increased again (P < 0.05 vs. aged control). In the Morris water maze, the EEBP animals had shorter latency (100 mg/kg) and had more crossing times (25 mg/kg) in seeking the platform position (P < 0.05, vs. aged control). The results suggested that EEBP could affect the spontaneous activity and improve memory in aged animals and could have potential advantages for cognition improvement in aged populations.

Nle3,d-Phe6]-γ2-melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2-melanocyte-stimulating hormone in anaesthetized rats

The present study compared the cardiovascular and renal actions of γ(2) -melanocyte-stimulating hormone (γ(2) MSH) with those of the synthetic analogue [Nle(3) ,d-Phe(6) ]-γ(2) MSH (NDP-γ(2) MSH) and explored the effects of high dietary salt intake on the renal actions of NDP-γ(2) MSH. Both peptides were infused systemically (3-1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high-salt (4% NaCl; HS) diet. Mean arterial pressure (MAP), glomerular filtration rate (GFR), urinary sodium excretion (U(N) (a) V), urinary output (UV) and fractional sodium excretion were determined, as was expression of the melanocortin MC(3) receptor in inner medullary collecting duct (IMCD) epithelial cells. Both renal and systemic infusion of γ(2) MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP-γ(2) MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP-γ(2) MSH increased U(N) (a) V and UV by two- to threefold in rats fed the normal salt diet and by six- to sevenfold in rats fed the HS diet. Furthermore, NDP-γ(2) MSH induced a 3.5-fold increase in GFR only in rats fed the HS diet. These renal effects of NDP-γ(2) MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5-fold increase in MC(3) receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP-γ(2) MSH induced the natriuretic but not the cardiovascular effects exhibited by γ(2) MSH. The renal activities may be attributed to a direct binding of NDP-γ(2) MSH to MC(3) receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.

Diuretic Effects of Cannabinoids

In vivo effects of cannabinoid (CB) agonists are often assessed using four well-established measures: locomotor activity, hypothermia, cataleptic-like effects, and analgesia. The present studies demonstrate that doses of CB agonists that produce these effects also reliably increase diuresis. Diuretic effects of several CB agonists were measured in female rats over 2 hours immediately after drug injection, and results were compared with hypothermic effects. Direct-acting CB1 agonists, including Δ(9)-tetrahydrocannabinol, WIN 55,212 [R-(1)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate], AM2389 [9β-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol], and AM4054 [9β-(hydroxymethyl)-3-(1-adamantyl)-hexahydrocannabinol], produced dose-dependent increases in diuresis and decreases in colonic temperature, with slightly lower ED(50) values for diuresis than for hypothermia. The highest doses of cannabinoid drugs yielded, on average, 26-32 g/kg urine; comparable effects were obtained with 10 mg/kg furosemide and 3.0 mg/kg trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50-488). Methanandamide (10.0 mg/kg) had lesser effect than other CB agonists, and the CB2 agonist AM1241 [1-(methylpiperidin-2-ylmethyl)-3-(2-iodo-5-nitrobenzoyl)indole], the anandamide transport inhibitor AM404, and the CB antagonist rimonabant did not have diuretic effects. In further studies, the diuretic effects of the CB1 agonist AM4054 were similar in male and female rats, displayed a relatively rapid onset to action, and were dose-dependently antagonized by 30 minutes pretreatment with rimonabant, but not by the vanilloid receptor type I antagonist capsazepine, nor were the effects of WIN 55,212 antagonized by the CB2 antagonist AM630 [(6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl) methanone)]. These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms.

Preliminary studies on diuretic effect of hygrophila auriculata (schum) heine in rats

Purpose: Hygrophila auriculata is a traditional folk medicine widely used in the treatment of urinary infection, gout, hepatic obstruction and as a diuretic. This study was conducted to examine the diuretic effect of whole plant extracts and its fractions. Methods: The diuretic effect was examined by treating different groups of wistar albino rats with single (200 mg/kg) oral doses of alcoholic extract/fractions. Frusemide (10 mg/kg) was used as positive control in the study. The urine volume and electrolyte concentration (Na+, K+ and Cl-) were measured. Results: Out of the different fractions and extract, the n-butanol fraction (200 mg/kg) significantly and markedly increased the urine output (p < 0.01). The pattern of diuresis induced by the n-butanol fraction was almost similar to that produced by the frusemide. Conclusion: Hygrophila auriculata plant extract posesses diuretic effects in rats. Keywords: Hygrophila auriculata, Diuretics, Electrolytes, Terpenoid.

Acute and chronic diuretic effect of ethanolic extract of leaves of &lt;I&gt;Cocculus hirsutus&lt;/I&gt; (L.) Diles in normal rats

The objective of this study was to evaluate the acute and chronic diuretic effect of the ethanolic extract of the leaves of Cocculus hirsutus (L.) Diles. The ethanolic extract was administered (100, 200 and 400 mg/kg, p.o.) in Wistar rats. In the acute study, rats received drugs orally and urine was collected after 1, 2, 3, 4, 5 and 6 h. The chronic study involved repeated administration of ethanolic extract for 28 days and urine was collected on day 1, 7, 14, 21 and 28. The parameters were total urine volume, concentration of Na+, K+ and Cl- ions, creatinine in urine and serum. Urine output, electrolytes (Na+, K+ and Cl- ions) and creatinine were determined on day 7, 14, 21 and 28. The highest dose (400 mg/kg) of the ethanolic extract significantly (P < 0.01) enhanced urine output. Excretion of cations (Na+ and K+ ions) and anions (Cl- ions) increased significantly with respect to the control (gum acacia 2% dissolved in saline, 10 ml/kg) group. The increase of cations in the urine after treatment with ethanolic extract was dose dependent. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) did not significantly change the concentration of Na+, K+ and Cl- ions in serum. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) increased the excretion of creatinine in urine but with a corresponding decrease in serum. It was concluded that the ethanolic extract of the leaves of C. hirsutus (400 mg/kg) had significant diuretic effect in rats.

Acute and chronic diuretic effect of ethanolic extract of leaves of Cocculus hirsutus (L.) Diles in normal rats

Abstract Objectives The objective of this study was to evaluate the acute and chronic diuretic effect of the ethanolic extract of the leaves of Cocculus hirsutus (L.) Diles. Methods The ethanolic extract was administered (100, 200 and 400 mg/kg, p.o.) in Wistar rats. In the acute study, rats received drugs orally and urine was collected after 1, 2, 3, 4, 5 and 6 h. The chronic study involved repeated administration of ethanolic extract for 28 days and urine was collected on day 1, 7, 14, 21 and 28. The parameters were total urine volume, concentration of Na+, K+ and Cl- ions, creatinine in urine and serum. Urine output, electrolytes (Na+, K+ and Cl- ions) and creatinine were determined on day 7, 14, 21 and 28. Key findings The highest dose (400 mg/kg) of the ethanolic extract significantly (P &amp;lt; 0.01) enhanced urine output. Excretion of cations (Na+ and K+ ions) and anions (Cl- ions) increased significantly with respect to the control (gum acacia 2% dissolved in saline, 10 ml/kg) group. The increase of cations in the urine after treatment with ethanolic extract was dose dependent. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) did not significantly change the concentration of Na+, K+ and Cl- ions in serum. The ethanolic extract of the leaves of C. hirsutus (100, 200 and 400 mg/kg) and furosemide (10 mg/kg) increased the excretion of creatinine in urine but with a corresponding decrease in serum. Conclusions It was concluded that the ethanolic extract of the leaves of C. hirsutus (400 mg/kg) had significant diuretic effect in rats.

Diuretic activity of some Withania aristata Ait. fractions

We previously reported on the significant dose-dependent diuretic effects produced in laboratory rats by hot water infusions and methanol extracts of Withania aristata Ait., where notable increases were observed in the excretion of water and sodium, with an interesting potassium-saving effect. The present study gives the results of the diuretic effects in rats of the hexane, dichloromethane, ethyl acetate, butanol and methanol–water fractions of the previously studied methanol extract. Water excretion rate, pH, density, conductivity and content of Na +, K + and Cl − were measured in the urine of the rats when subjected to hypersaline conditions. Of the above fractions, the methanol:water extract (100 mg/kg) showed the most interesting diuretic activity (25%; ** p < 0.01), which suggested that increase in the polarity of the extracting solvent led to an increase in the concentration of the polar compounds responsible for the diuretic effect. These data, together with previous results on the aqueous and methanol extracts, reaffirm assertions made regarding the effectiveness of the extracts of this plant against urinary pathologies in the Canary Islands folk medicine.

Synthesis and structure-activity relationships of 5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepine derivatives: novel arginine vasopressin antagonists.

A variety of novel heterocyclic compounds having thienoazepine, pyrroloazepine, furoazepine, and thienodiazepine skeletons were synthesized, most of which exhibited potent antagonism of [(3)H]-AVP specific binding in assays using rat liver (V1), rat kidney (V2), human platelet plasma membranes, and recombinant human CHO cells (V2), as well as antagonizing AVP-induced hypertension in rats (V1, intravenous) and showing a diuretic effect in rats (V2, oral). By detailed studies of the structure-activity relationships of these compounds, the thienoazepine derivative 1 was found to be a very potent combined V1 and V2 antagonist. After further pharmacological and toxicological evaluation as well as physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for clinical studies as a potent AVP antagonist with a long duration of action.

Chronic diuretic effect of the water extract of Spergularia purpurea in normal rats

The purpose of this study was to examine the chronic diuretic effect of the water extract of the whole plant of Spergularia purpurea (SP) at different doses (100, 200 and 400 mg/kg) in normal rats. Daily oral administration of the water extract was tested for 4 weeks. Urinary water and electrolytes excretion were determined weekly. Oral administration of the water extract at different doses produced a significant and dose-dependent diuresis and increase in electrolytes excretion. The highest dose (400 mg/kg) of the water extract of SP enhanced urine output from 7.15±0.42 ml/24 h at the start to 23.01±0.75 ml/24 h after 4 weeks (p<0.001). It also produced significant increase in urinary excretion of Na + ( P<0.01), K + ( P<0.01) and Cl − ( P<0.01). Chronic treatment with SP decreased significantly urine osmolality ( P<0.01 vs. control), while a slight increase in glomerular filtration rate was also observed ( P<0.05) for both doses of water extract (100 and 400 mg/kg). It is concluded that the water extract of whole plant of SP has a significant diuretic effect in rats.

Epidermal growth factor and fluid and electrolyte balance in the rat.

Epidermal growth factor (EGF) has been shown to induce a renal diuresis and natriuresis in sheep and stimulate prostaglandin synthesis from inner rat medullary collecting duct cells in culture. The aims of our study were 1) to investigate whether the renal effects of intravenous infusion of EGF were species specific and 2) to determine the mechanism of these effects by studying the interaction between EGF and indomethacin (a prostaglandin synthase inhibitor) in the conscious rat. Sprague-Dawley rats received intravenous infusions of either 0.9% saline or 0.2 or 2.0 micrograms EGF.kg-1.h-1 over a 6-day period after an initial baseline period. Infusion of 2.0 micrograms EGF.kg-1.h-1 caused an increase in urine volume (baseline: 5.5 +/- 0.2 ml to day 5: 9.0 +/- 0.4 ml, P < 0.01) and corresponding polydipsia, but not natriuresis. Administration of indomethacin with 2.0 micrograms EGF.kg-1.h-1 attenuated (P < 0.05) the diuretic (day 5 EGF + vehicle: 12.2 +/- 1.1 ml vs. EGF + indomethacin: 8.7 +/- 0.9 ml) and polydipsic effects of EGF. These studies demonstrate that intravenous infusion of EGF causes a diuretic effect in rats without natriuresis and that prostaglandins play a role in the diuretic effect of EGF in the rat.

Central and peripheral actions of the novel kappa-opioid receptor agonist, EMD 60400.

1. The pharmacological characteristics of the kappa-opioid receptor agonist, EMD 60400, have been investigated, with particular reference to its central and peripheral sites of action and its ability to influence nociception. The kappa agonists ICI 197067 and ICI 204448 were tested for purposes of comparison. 2. EMD 60400 and ICI 197067 bind with high affinity (IC50 values of 2.8 and 1.5 nM, respectively) and high selectivity to kappa-opioid receptors. ICI 204448 has a lower binding affinity (IC50 13.0 nM) and selectivity for kappa-opioid receptors. 3. EMD 60400, ICI 197067, and ICI 204448 are full and potent agonists in the rabbit vas deferens in vitro assay for kappa-opioid receptors (IC50 values of 41.8, 15.7 and 15 nM, respectively). 4. Ex vivo binding experiments in mice revealed that EMD 60400 and ICI 197067 were well taken up after s.c. administration. Brain levels of EMD 60400 were lower than those of ICI 197067 at comparable doses, indicating that EMD 60400 does not penetrate into the CNS as well as ICI 197067. 5. Haloperidol-induced DOPA accumulation in the nucleus accumbens of the rat was dose-dependently reversed by s.c. application of EMD 60400 and ICI 197067 at doses of and above 3 and 0.3 mg kg-1, respectively. ICI 204448 had no effect on DOPA accumulation at 30 mg kg-1, s.c. 6. Prolongation of hexobarbitone-induced sleeping time in mice and motor impairment in the rat rotarod test were observed for EMD 60400 at doses above 3 and 2.5 mg kg-1, s.c., respectively, and for ICI 197067 at doses above 0.3 and 0.25 mg kg-1, s.c., respectively. ICI 204448 was inactive in these tests at doses of 30 and 100 mg kg-1, s.c., respectively.7. EMD 60400 applied s.c. produced dose-dependent naloxone-reversible antinociception in the mouse formalin test (1st and 2nd phase ID50 0.44 and 0.47 mg kg-1, respectively) and rodent writhing test (ID50 mouse 0.55 mg kg-1 and rat 0.3mg kg-1). Furthermore, EMD 60400 was considerably more potent in the rat pressure pain test after the induction of inflammation with carrageenin than under normalgesic conditions (ID50 values 0.1 Microg kg-1 and 4.0 mg kg-1, s.c., respectively). The action of EMD 60400 (50 microgkg-1, s.c.) in the hyperalgesic pressure pain test was completely antagonized by injection of the K-opioid antagonist, norbinaltorphimine (100 microg) into the inflamed tissue, thus demonstrating the peripheral opioid nature of this effect.8. EMD 60400 produced dose-dependent inhibition of neurogenic plasma extravasation elicited byantidromic electrical stimulation of the rat saphenous nerve (ID50 value 0.3 mg kg-1, i.v.). This inhibition was completely antagonized by intraplantar injection of norbinaltorphimine (50 microg).9. EMD 60400, ICI 197067, and ICI 204448 have diuretic effects in rats at doses of and above 0.1, 0.01,and 0.3 mg kg-1, s.c., respectively. An antidiuretic action was also observed with ICI 197067 at very low doses (3 and 6 microgkg-1, s.c.).10. Pharmacological and biochemical data therefore indicate that the three K-opioid receptor agonists tested here have different tendencies to elicit centrally-mediated sedation and putative aversion(ICI 197067 > EMD 60400 > ICI 204448) which correspond to their ability to cross the blood-brain barrier. EMD 60400 combines high affinity and selectivity for the K receptor with a degree of peripheral selectivity. The peripheral actions of systemically-applied EMD 60400 against hyperalgesic pressure pain and neurogenic inflammation are very probably mediated by opioid receptors on the endings of sensory nerve fibres.

Pharmacological evaluation of the glycosidated phenylpropanoids containing fraction fromOrobanche crenata

Ethylacetate fraction fromOrobanche crenata, contained two phenylpropanoid glycosides, exhibited some pharmacological properties. It was found to be non-toxic to rats in oral doses up to 500mg/100gm body weight. In large doses, it lowered the arterial blood pressure of anaethetised rats, and produced significant analgesic effect in mice and diuretic effect in rats. It further showed smooth muscle relaxant and antispasmodic effects in the isolated rabbit intestine and guinea-pig ileum respectively.