[Adsorption of Residual Pesticide Glyphosate Isopropylamine in Surface Water by Modified Biomass Materials].

Effective treatment of pesticide residue-induced pollution in the aqueous environment is the key to improving the water quality of rivers and lakes. Modified biomass material (Fe-Al-PS) was successfully prepared by impregnating Fe and Al bimetallic compounds to peanut shell powder for adsorption of glyphosate isopropylamine salt herbicide residues in aqueous environments. Fe-Al-PS reached adsorption equilibrium for 10 mg·L-1 of glyphosate isopropylamine salt at the adsorbent dosage and adsorption time of 0.14 g and 10 min, respectively, and the removal rates were stabilized at 99.9 % and 99.6 %, respectively. The adsorption process followed the pseudo-secondary kinetic and Freundlich adsorption isotherm models and belonged to multi-molecular layer chemisorption. The removal of glyphosate isopropylamine salt by Fe-Al-PS was greater than 95 % in a wide range of pH (2-11). The thermodynamic results indicated that the adsorption was a spontaneous exothermic process. Fe-Al-PS materials were easy to access and involved simple synthesis and low energy consumption, had high anti-interference ability, were reusable, and could be used not only for the effective removal of glyphosate isopropylamine salt herbicide in real water bodies but also for the removal of inorganic phosphorus.

Biotransamination of Furan-Based Aldehydes with Isopropylamine: Enzyme Screening and pH Influence.

Furan-based amines are highly valuable compounds which can be directly obtained via reductive amination from easily accessible furfural, 5-(hydroxymethyl)furfural (HMF) and 2,5-diformylfuran (DFF). Herein the biocatalytic amination of these carbonyl derivatives is disclosed using amine transaminases (ATAs) and isopropylamine (IPA) as amine donors. Among the different biocatalysts tested, the ones from Chromobacterium violaceum (Cv-TA), Arthrobacter citreus (ArS-TA), and variants from Arthrobacter sp. (ArRmut11-TA) and Vibrio fluvialis (Vf-mut-TA), afforded high levels of product formation (>80 %) at 100-200 mM aldehyde concentration. The transformations were studied in terms of enzyme and IPA loading. The pH influence was found as a key factor and attributed to the imine/aldehyde equilibrium that can arise from the high reactivity of the carbonyl substrates with a nucleophilic amine such as IPA.

Organically Templated Uranyl Sulfates and Selenates: Structural Complexity and Crystal Chemical Restrictions for Isotypic Compounds Formation.

This paper reviews the state of the art in the structural chemistry of organically templated uranyl sulfates and selenates, which are considered as the most representative groups of U-bearing synthetic compounds. In total, there are 194 compounds known for both groups, the crystal structures of which include 84 various organic molecules. Structural studies and topological analysis clearly indicate complex crystal chemical limitations in terms of the isomorphic substitution implementation, since the existence of isotypic phases has to date been confirmed only for 24 compounds out of 194, which is slightly above 12%. The structural architecture of the entire compound depends on the combination of the organic and oxyanion parts, changes in which are sometimes realized even while maintaining the topology of the U-bearing complex. An increase in the size of the hydrocarbon part and number of charge functional groups of the organic cation leads to the formation of rare and more complex topologies. In addition, the crystal structures of two novel uranyl sulfates and one uranyl selenate, templated by isopropylammonium cations, are reported.

Intralipid and caffeic acid phenethyl ester reverse the neurotoxic effects of organophosphate poisoning in rats.

Background: Organophosphate (Op)-containing herbicides continue to be widely used in the world. Although its usage and intoxication are widespread, the studies on organophosphate-induced neurotoxicity and treatment protocols are very few in the literature. Aims: This study aimed to investigate any potential effects of caffeic acid phenyl ester with/without intralipid on neurotoxicity produced by acute intoxication of glyphosate isopropylamine in an experimental rat model. Materials And Methods: Forty-nine wistar albino rats were randomly allotted into seven experimental groups: I, control; II, intralipid (IL); III, caffeic acid phenyl esther (CAPE); IV, glyphosate isopropylamine (GI); V, GI + IL; VI, GI + CAPE; and VII, GI + IL + CAPE. Total antioxidant and oxidant status levels were gauged, and the oxidative stress index was calculated in the serum samples. On the other hand, the tissues were analyzed with hematoxylin-eosin (HE) staining protocol and counted up by immunohistochemical method. Statistical evaluations were conducted using SPSS 11.5 for Windows (SPSS, Chicago, IL, USA). Results: Compared to the control, IL, and GI + IL + CAPE groups, the GI group significantly decreased the total antioxidant levels in brain tissues. In a supportive nature, a significant increase in the oxidative site index (OSI) in the GI group compared to other groups. Especially standing out point of these findings is the significant difference between the GI + IL + CAPE and the GI group. Parallelly, histopathological analysis extended severe neurotoxicity in the GI group. Neurotoxic status was reduced significantly in the GI + CAPE + IL group. The histopathologic examinations confirmed biochemical results. The results also revealed that CAPE and IL, probably their antioxidant effects, have a rehabilitative effect on neurotoxicity caused by GI. Conclusion: Therefore, CAPE and IL may function as potential cleansing and scavenger agents for supportive therapy regarding tissue damage or facilitate the therapeutic effects of the routine treatment of the patient with GI poisoning.

Copper(II) Perfluorinated Carboxylate Complexes with Small Aliphatic Amines as Universal Precursors for Nanomaterial Fabrication.

Copper(II) carboxylate compounds with ethylamine and isopropylamine of the general formula [Cu2(RNH2)2(µ-O2CRf)4], where R = Et, iPr, and Rf = CnF2n+1, n = 1-6, were characterised in the condensed and gas phases by electron impact mass spectrometry (EI MS), IR spectroscopy, and thermal analysis. A mass spectra analysis confirmed the presence of metallated species in the gas phase. Among the observed fragments, the pseudomolecular ions [Cu2(RNH2)2(µ-O2CRf)3]+ were found, which suggests the dimeric structure of the studied complexes with axially N-coordinated ethyl- or isopropylamine molecules and bridging perfluorinated carboxylates. TGA studies demonstrated that copper transfer to the gas phase occurs even under atmospheric pressure. The temperature range of the [Cu2(RNH2)2(µ-O2CRf)4] and other copper carriers detection, observed in variable temperature infrared spectra, depends on the type of amine. The possible mechanisms of the decomposition of the tested compounds are proposed. The copper films were produced without additional reducing agents despite using Cu(II) CVD precursors in the chemical vapor deposition experiments. The layers of the gel-like complexes were fabricated in both spin- and dip-coating experiments, resulting in copper or copper oxide materials when heated. Dinuclear copper(II) carboxylate complexes with ethyl- and isopropylamine [Cu2(RNH2)2(µ-O2CRf)4] can be applied for the formation of metal or metal oxide materials, also in the nanoscale, by vapour and 'wet' deposition methods.

Does the Anionic Surfactant Isopropylamine Dodecylbenzene Sulfonate Induce Hepatic Oxidative Stress and Impairment in Carassius auratus gibelio?

Isopropylamine dodecylbenzene sulfonate (IDS) is a new kind of anionic surfactant (ANS). To preliminarily evaluate the aquatic toxicity of IDS, this study took gibel carp (Carassius auratus gibelio) as the research object. The well-acclimatized fish were divided into six groups and exposed to 0 mg/L, 0.5 mg/L, 1.0 mg/L, 2.0 mg/L, 4.0 mg/L, or 8.0 mg/L of IDS for 7, 14, 21 or 28 days. Our results showed that the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the liver were unaffected by IDS exposure, while glutathione peroxidase (GSH-Px) activity was significantly inhibited. Hepatic tissue exhibited pathological damage, characterized by nuclear migration and dissolution and cell boundary blurring. The results suggest that IDS does not cause oxidative stress in the liver, but cause hepatic histopathological damage. GSH-Px can be considered as a biomarker of IDS exposure in gibel carp.

[Industrial adaptability selection for a novel ω-transaminase].

ω-transaminase (ω-TA) is the most promising biocatalyst for chiral amine synthesis. However, most wild-type ω-TAs cannot be applied in industry directly due to their low stability and unfavorable reaction equilibrium. In order to discover a novel ω-TA for industrial application, we designed a procedure of adaptive selection, including the screening of substrates, protein sequences and clones, enzyme activity, and product conversion and characterization, as well as trouble-shooting of each step. Through this procedure, we screened a novel ω-TA, ATA-W12 of Caulobacter sp. from a soil metagenome. The strain could convert 20 mmol/L 1-Boc-3-pyrrolidinone and 20 mmol/L 1-Boc-3-piperidone with 85.84% and 67.42% conversion rate, respectively, in a 1-mL scale with isopropylamine (IPA) as amine donor. ATA-W12 maintained 100% activity at 40 °C for 168 h, and its optimal reaction condition is at pH 8.5 and 40 °C. These excellent properties benefit the application of IPA as an ideal amino donor in industry. We scaled up the production of (S)-(+)-1-boc-3-aminopiperidine up to 50 mL (100 g/L) scale with this novel biocatalyst for its further industrial application.

Glyphosate-resistant soybeans yield in function of glyphosate salts, doses and stadium phenological / Produtuvidade de cultivares de soja em função dos sais de glyphosate, doses e épocas de aplicação

Given the importance of soybean to the global economy and as a food source, improving crop management techniques is integral to obtaining higher yields. As such, this study aimed to assess the yield of soybean cultivars as a function of different glyphosate salt formulations, doses and application times. Two field experiments were conducted simultaneously using a randomized block design and 3x4x2 factorial scheme, with three repetitions. Factor A consisted of three glyphosate formulations: isopropylamine salt (Roundup Original®), ammonium salt (Roundup WG®), and potassium salt (Zapp Qi®), factor B four application times: 0, 14, 28, 42 days after planting (DAP), and factor C two doses: the recommended dose of 720 grams of acid equivalent per hectare and twice that (1440 grams of acid equivalent per hectare). There was no difference between the glyphosate salts for the BMX Ativa RR® cultivar, but yields of BMX Apolo RR® submitted to ammonium salt were 28% higher than those recorded for the other salts studied. Glyphosate potassium salt resulted in lower soybean yields. Potassium salt application between 14 and 28 DAP caused greater toxicity in both the soybean cultivars analyzed.

Diante da importância da cultura da soja tanto na economia mundial quanto para a alimentação, a melhoria das técnicas de cultivo torna-se um ponto fundamental na obtenção de maiores produtividades. Desta forma o objetivo do trabalho foi avaliar a produtividade de cultivares de soja sob a influência da aplicação de diferentes sais de glyphosate, doses e épocas de aplicação. Dois experimentos de campo foram realizados simultaneamente em delineamento de blocos casualizados com arranjo trifatorial (3x4x2) com três repetições. O fator A consistiu de três formulações de glyphosate: sal de isopropilamina (Roundup Original®), sal de amônio (Roundup WG®), sal de potássio (Zapp Qi®). O fator B consistiu de quatro épocas de aplicação: 0, 14, 28, 42 dias após a semeadura (DAS). O fator C consistiu em duas doses: a dose recomendada de 720 gramas de equivalente ácido por hectare e duas vezes a dose recomendada com 1440 gramas de equivalente ácido por hectare. Para a cultivar BMX Ativa RR® não se observou diferença quanto aos sais, porém a cultivar BMX Apolo RR® submetida a aplicação de sal de amônio demostrou uma produtividade 28% superior em relação aos demais sais. O glyphosate na formulação sal de potássio apresentou redução da produtividade da cultura da soja. Aplicações de glyphosate na formulação sal de potássio realizadas entre os 14 e 28 dias após a semeadura causam maior toxidez em ambas cultivares de soja utilizadas.

Hormetic effect of glyphosate persists during the entire growth period and increases sugarcane yield.

BACKGROUND: Stimulation of plant growth by low doses of a toxic compound is defined as a hormetic effect. Exposure of plants to low doses of glyphosate can cause stimulatory effects on growth or other variables. Sugarcane is the major biofuel and sugar-production crop cultivated in Brazil, but its expansion to new areas is limited; therefore, there is a demand for new technologies to improve sugarcane production per unit area. The use of pesticides to stimulate growth through the hormetic effect might be a suitable strategy to increase sugarcane yields. The purpose of this research was to investigate the effect of a low dose of glyphosate on metabolic compound accumulation, leaf phosphorus (P) concentration, and morphological variables across a one-year sugarcane cycle, as well as to determine whether the glyphosate effect was sustained and effective in improving the yield and technological quality of the sugarcane at harvest. RESULTS: The application of a low dose of glyphosate led to higher concentrations of shikimic acid and quinic acid, higher leaf P concentrations, and improved plant growth, yield, and technological quality of the sugarcane, by increasing the Brix% juice, pol% cane, total recoverable sugar, tons of culms per hectare, and tons of pol per hectare, relative to the results for an untreated control. CONCLUSIONS: The increased growth stimuli, observed through several variables, promoted an improvement in sugarcane yield. Therefore, the application of a low dose of glyphosate to sugarcane is a promising practice for crop management. © 2020 Society of Chemical Industry.

Determination of acute oral toxicity of glyphosate isopropylamine salt in rats.

In this study, we aim to determine the median lethal dose (LD50) of glyphosate isopropylamine salt (GI), which is commonly used in the world and especially in Turkey against to weeds, in male and female rats by using the probit or logit analysis method. A total of 140 Wistar rats were used, including 70 females and 70 males. To determine LD50, the male and female rats were randomized into 7 groups made up of 10 animals in each group. At doses of 6000, 6500, 7000, 7500, 8000, 8500, and 9000 mg / kg, GI was administered to the male and female rats by oral gavage. After dosing, the animals were periodically monitored for 14 days. No deaths were observed after 48 h of herbicide application. In this study, only logit analysis was used for the LD50 value to be calculated in the male rats within 24 h, while other analyses were carried out with the probit method. In the female and male rats, the LD50 levels of GI between 24 and 48 h were determined as 7444.26-7878.50 mg/kg and 7203.58-7397.25 mg/kg, respectively. According to these results, it was concluded that female rats are more sensitive to GI than male rats. We believe that the findings that were obtained will guide researchers, clinicians, and toxicologists through preventive and curative studies against acute poisoning that may occur with GI.

Roundup-Induced AMPK/mTOR-Mediated Autophagy in Human A549 Cells.

The extensive use of pesticide caused an amount of pressure on the environment and increased the potential human health risk. Glyphosate-based herbicide (GBH) is one of the most widely used pesticides based on a 5-enolpyruvylshikimate-3-phosphate synthase target, which does not exist in vertebrates. Here, we study autophagic effects of the most famous commercial GBH Roundup (RDP) on human A549 cells in vitro. Intracellular biochemical assay indicated opening of mitochondrial permeability transition pore, LC3-II conversion, up-regulation of beclin-1, down-regulation of p62, and the changes in the phosphorylation of AMPK and mTOR induced by RDP in A549 cells. Further experimental results indicated that all the effects induced by RDP were related to its adjuvant polyethoxylated tallow amine, not its herbicidal active ingredient glyphosate isopropylamine salt. All these results showed that RDP has the ability to induce AMPK/mTOR-mediated cell autophagy in human A549 cells. This study would provide a theoretical basis for understanding RDP's autophagic effects on human A549 cells and attract attention on the potential human health risks induced by the adjuvant.

Antioxidant and cytoprotective effects of N-acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats.

It is claimed that oxidative stress has a prominent role in the mechanism of toxic effects formed by glyphosate-based herbicide (GBH) in living systems. A strong thiol compound, N-acetylcysteine (NAC), has antioxidative and cytoprotective properties. The objective in this subchronic toxicity study was to identify the prophylactic effect of NAC over histopathological changes and oxidative stress induced by GBH in blood, renal, liver, cardiac, and brain tissues. A sum of 28 male Wistar rats were divided into four equal groups, each containing 7 rats. During the study, group I (control group) was supplied with normal rodent bait and tap water ad libitum. The applied agents were 160 mg/kg NAC to group II, 375 mg/kg as equivalent to 1/10 of lethal dose 50% (LD50) of GBH to group III, and 160 mg/kg of NAC and 375 mg/kg of GBH together once per day as oral gavage to group IV for 8 weeks. While GBH decreased the levels of GSH in blood, liver, kidney, and brain tissues, it considerably increased malondialdehyde levels. On the contrary, these parameters happened to improve in the group supplied with NAC. Besides, it was seen that NAC was observed to improve the histopathologic changes in rat tissues induced by GBH. It was concluded that NAC protects oxidative stress and tissue damage induced by GBH in blood and tissue and this prophylactic effect could be attributed to its antioxidant and free radical sweeper character.

Glyphosate ingestion causing multiple organ failure: a near-fatal case report.

A 55 years old man self-presented to our Emergency Department (ED) reporting an attempted suicide by cutting the left forearm veins and ingesting approximately 200 mL of an herbicide (Myrtos®, containing 36% of glyphosate as isopropylamine salt). Laboratory tests showed metabolic acidosis. Hydration with normal saline and alkalinization with sodium bicarbonate was started according to suggestion of the poison control center, since an antidote was unavailable. Cardiorespiratory condition gradually worsened, so that non-invasive positive pressure ventilation (NIPPV) was applied and infusion of fluids was established. Nevertheless, the patient deteriorated and he needed to be transferred to the Intensive Care Unit (ICU), where he underwent orotracheal intubation and invasive mechanical ventilation. Noradrenaline and adrenaline were infused and fluid resuscitation with crystalloids was incremented. An esophagogastroduodenoscopy (EGD) showed diffuse mucosal erosions of upper digestive tract. No signs of visceral perforation were found during ICU stay. In the following days, the clinical conditions improved and a new EGD showed marked improvement of erosive lesions. After 12 days of ICU stay, the patient was extubated and then transferred to the Psychiatric Unit, in good clinical conditions. Gliphosate ingestion is associated with rapid development of multiple organ failure (MOF). Since an effective antidote is unavailable, major attention should be placed to aggressive life-support care and careful monitoring of complications.

Efficient synthesis of D6 -clenproperol and D6 -cimaterol using deuterium isopropylamine as labelled precursor.

This report presents an efficient synthesis of D6 -clenproperol and D6 -cimaterol with 99.5% and 99.7% isotopic abundance in acceptable yields and excellent chemical purities with deuterium isopropylamine as labelled precursor. Their structures and the isotope-abundance were confirmed by proton nuclear magnetic resonance and liquid chromatography-mass spectrometry.

Synthesis of 3-aroyl-4-aryl-1-isopropylamino-4-piperidinols and evaluation of the cytotoxicities of the compounds against human hepatoma and breast cancer cell lines.

Some 4-piperidinol derivatives were synthesized and their cytotoxicity was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. Aryl part was changed as phenyl in 2a, 4-methylphenyl in 2b, 4-methoxyphenyl in 2c, 4-chlorophenyl in 2d, 4-fluorophenyl in 2e, 4-bromophenyl in 2f, 4-nitrophenyl in 2g and 2-thienyl in 3. Compounds were synthesized and reported for the first time by this study except 2a and 2d. Chemical structures were confirmed by (1)H NMR, (13)C NMR, IR, MS and elemental analyses. Compounds 2a (3.1 times), 2c (3.8 times), 2f (4.6 times), 2g (1.3 times) and 3 (3.2 times) had 1.3-4.6 times higher cytotoxic potency than the reference compound 5-FU against Huh7 cell line while all the compounds synthesized had shown lower activities against T47D cell line than 5-FU. In the light of these results, compounds 2a, 2c, 2f, 2g and 3 may serve as model compounds for further studies.

The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10µM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10µM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200µM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10µM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

Nitroxyl donors retain their depressor effects in hypertension.

Nitroxyl (HNO), the redox congener of nitric oxide, has numerous vasoprotective actions including an ability to induce vasodilation and inhibit platelet aggregation. Given HNO is resistant to scavenging by superoxide and does not develop tolerance, we hypothesised that HNO would retain its in vivo vasodilatory action in the setting of hypertension. The in vitro and in vivo vasodilator properties of the HNO donors Angeli's salt (AS) and isopropylamine/NONOate (IPA/NO) were compared with the NO donor diethylamine/NONOate (DEA/NO) in spontaneously hypertensive rats (SHR) and normotensive [Wistar-Kyoto (WKY) rats]. AS (10, 50, and 200 µg/kg), IPA/NO (10, 50, and 200 µg/kg), and DEA/NO (1, 5, and 20 µg/kg) caused dose-dependent depressor responses in conscious WKY rats of similar magnitude. Depressor responses to AS and IPA/NO were significantly attenuated (P < 0.01) after infusion of the HNO scavenger N-acetyl-l-cysteine (NAC), confirming that AS and IPA/NO function as HNO donors in vivo. In contrast, responses to DEA/NO were unchanged following NAC infusion. Depressor responses to AS and IPA/NO in conscious SHR retained their sensitivity to the inhibitory effects of NAC (P < 0.01), yet those to DEA/NO in SHR were significantly (P < 0.05) enhanced following NAC infusion. Importantly, depressor responses to AS, IPA/NO, and DEA/NO were preserved in hypertension and vasorelaxation to AS and DEA/NO, in isolated aorta, unchanged in SHR as compared with WKY rats. This study has shown for the first time that HNO donors exert antihypertensive effects in vivo and may, therefore, offer a therapeutic alternative to traditional nitrovasodilators in the treatment of cardiovascular disorders such as hypertension.

Quantitative detection of nitroxyl upon trapping with glutathione and labeling with a specific fluorogenic reagent.

Donors of nitroxyl (HNO) have shown promise for treatment of stroke, heart failure, alcoholism and cancer. However, comparing the pharmacological capacities of various donors is difficult without first quantifying the amount of HNO released from each donor. Detection and quantitation of HNO has been complicated by the rapid self-consumption of HNO through irreversible dimerization, poor selectivity of trapping agents against other nitrogen oxides, and/or low sensitivity towards HNO. Here, an assay is described for the trapping of HNO by glutathione (GSH) followed by labeling of GSH with the fluorogenic agent, naphthalene-2,3-dicarboxaldehyde (NDA), and subsequent quantitation by fluorescence difference. The newly developed assay was used to validate the pH-dependence of HNO release from isopropylamine NONOate (IPA/NO), which is a dual donor of HNO and NO at physiological pH. Furthermore, varied assay conditions were utilized to suggest the ratios of the products of the reaction of GSH with HNO. At intracellular concentrations of GSH, the disulfide (GSSG) was the major product, but significant concentrations of glutathione sulfinamide (GS(O)NH2) were also detected. This suggests that GS(O)NH2, which is a selective biomarker of HNO, may be produced in concentrations that are amenable to in vivo analysis.

HYPOTENSIVE ACTION OF ISOPROPYLAMINE VANILLINATE / 中国药理学通报

I sopropylmine vanillinate (IV) given iv 5 , 10 mg/kg in anesthe tized rats produced a dose-dependent decrease in mean arterial pressure and a concomitant decrease in heart rate.In pithed rats IV was unable to shift the phenylephrine doserespon-se curve to the right, but prazosine caused 53-fold shift.No direct effect of vasodilation was shown by IV on rabbit aorta strips .The concentration-response curve of isoprenaline in isolated rat right atrium was competitively inhibited by IV and propranolol. pA2 value was 4.0 for IV and 8.2 for propranolol. In addition, 'IV depressed contractility & heart rate of isolated rat atria.These results suggest that the hypotensive action of IV may be related to the decrease of HR, inhibition of contractility and slight blocking of B-adrenergic receptor. However the mechanism underlying the hypotensive effect of IV is to be further studied.