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Biomedical subjects

V Bauer

Publications and source records attributed to V Bauer.

At least 19 recordsLinked to original sources
PubMed2005

Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants.

Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)-diabetic rats in a 8-month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ-diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (D,L-alpha-tocopheryl acetate, 400-500 IU/kg/day) or ST plus vitamin E through an intra-oral catheter for a 8-month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1-64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline-induced contractions to basal levels. The tension induced by 120 mm KCl was not statistically different among the experimental groups. In normal rats, EFS-induced contractions were significantly inhibited by pyrogallol (10(-4) m), a free-radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)-induced contractions in ring sections was 48 +/- 5.8 in control, 75 +/- 5.5 in untreated-diabetic, 54 +/- 2.7 in ST-treated diabetic, and 58 +/- 4.7 in vitamin E-treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 +/- 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.

Animals↗
PubMed2003

[Referral by a general practitioner versus self-referral to a specialist practice. A comparison using chronic venous insufficiency as an example].

BACKGROUND AND OBJECTIVE: The gate-keeping role of general practitioners (GPs) is currently the topic of much debate in Germany. Currently it is possible for patients in Germany to see a specialist either through referral by their GP or directly through self-referral. To determine whether the gate-keeping role of GPs has a filtering effect, we compared patients referred by their GPs with self-referred patients presenting with suspected chronic venous insufficiency (CVI) to a specialist practice. PATIENTS AND METHODS: From September to December 2001, we prospectively recruited 316 patients seen for suspected CVI in a specialist practice for vascular surgery and phlebology. Symptoms and clinical findings were recorded using a standardized form. RESULTS: 58.2 % of patients were referred by their GPs. These patients were on average 6 years older and presented at a more advanced stage of disease than self-referred patients. No difference was found between patients with and without referral with respect to the symptoms reported or the therapy recommended by the specialist. CVI was excluded in 7.1 % of patients with a referral and in 6.8 % of those without a referral. CONCLUSIONS: The majority of patients consulting a specialist were referred by their GP. The more advanced disease stage of these patients indicates that a filtering process occurs in referral by GPs. However, the share of patients without referrals in whom CVI could be excluded was low and not significantly different from that of patients with referrals. This indicates that misdiagnosis due to self-referral is relatively modest. A cost reduction effect in a gate-keeper system could therefore only be small.

Adult↗
PubMed2003

Involvement of L-arginine-nitric oxide system in the response of isolated trachea to reactive oxygen species.

The aim of this study was to investigate the effect of reactive oxygen species (ROS), generated by electrolysis of Krebs-Henseleit solution (GE-KHS), on isolated guinea pig trachea and to assess the possible involvement of nitric oxide (NO) in the observed effects. The isolated trachea was superfused in GE-KHS, generating H2O2 and hypochlorous acid (HOCl), both of which slowly increased in the organ bath and reached final stable concentrations of 42 and 63 microM, respectively, at the rate of 20 ml/min(-1), and 261 and 245 microM, respectively, at the rate of 5 ml/min(-1). ROS GE-KHS-induced relaxation of tracheal rings was preceded by a small transient contraction in 40% and 65% of experiments when tracheal rings were superfused at the rate of 20 ml/min(-1) and 5 ml/min(-1), respectively. Removal of tracheal epithelium abolished the relaxation of the trachea induced by ROS GE-KHS and unmasked or potentiated trachealis contraction. The ROS GE-KHS-induced changes in trachealis tension were accompanied by an increase in thiobarbituric acid reactive substances (TBARS) and a decrease in nonprotein (NP) thiols in the trachea. These changes were inhibited by treatment with the antioxidant N-acetylcysteine (100 microM). Pretreatment of tracheal rings with the inhibitor of NO synthase (NOS) N(omega)-nitro-L-arginine (L-NOARG; 100 microM) for 20 min prior to exposure to ROS GE-KHS decreased the ROS GE-KHS-induced relaxation. When L-NOARG (100 microM) was present in the superfusing solution, not only 20 min before but also during superfusion with ROS GE-KHS, the evoked trachealis relaxation was reduced in the first 15 min but was enhanced in the 30th min. This late enhancement of relaxation was accompanied by a 12-fold increase in nitric oxide metabolites (NO(x)). ROS GE-KHS-induced elevation of TBARS levels in the trachea was decreased to 63% by pretreatment with L-NOARG (100 microM). Elevation of TBARS levels induced by incubation of brain liposomes with a hydroxyl radical generating system was decreased to 90% by L-NOARG (10, 100 microM), while the antioxidant stobadine (100 microM) nearly completely inhibited the evoked lipid peroxidation. In comparison with Trolox, L-NOARG exerted a slight scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl radical. The presence of L-arginine and D-arginine in the superfusion fluid for 15-20 min before and during exposure of the trachea to ROS GE-KHS inhibited trachealis relaxation. Results indicate that epithelium derived NO may participate in the response of guinea pig trachea to ROS GE-KHS. The presence of L-NOARG in the bathing fluid during superfusion with ROS GE-KHS gave rise to NO(x), with relaxing activity. L- and D-arginine induced an inhibition of the relaxatory response to ROS GE-KHS and partially prevented a ROS-induced decrease in NP thiols. The involvement of the small antioxidant effects of L-NOARG and L- and D-arginine in the above mentioned actions of L-NOARG and L-arginine requires additional investigation.

Acetylcysteine↗
PubMed2003

The effects of H2O2 on electromechanical activity of the ileum longitudinal muscle.

The effects of H2O2 on electrical and mechanical activity of the longitudinal layer from the guinea-pig ileum were studied using sucrose-gap technique and the influence of H2O2 on ionic current was investigated in single smooth muscle cells by the patch-clamp method. In most of the preparations tested, the spontaneous activity observed was composed of slow waves with superimposed action potentials (APs). Both were resistant to tetrodotoxin and atropine. H2O2 (1 mmol/l) evoked sustained 3-5 mV membrane depolarisation, doubled the amplitude of the slow waves and increased their frequency, augmented the APs and reduced their splitting. These changes were accompanied with significant contraction, which had an amplitude comparable to that of the tonic component of 50 mmol/l K+-induced contraction. Calcium-free solution caused membrane depolarisation, reduction of the slow wave amplitude and frequency, disappearance of APs and decreased the mechanical tension of the preparations. Application of H2O2 (1 mmol/l) into the zero-calcium bath solution recovered the APs, which was accompanied by a low amplitude contraction. H2O2 (up to 1 mmol/l) increased the L-type calcium current (I(Ca)) both under conventional whole-cell patch-clamp configuration and under amphotericin-perforated patches by 16 +/- 3%. These data demonstrated that contractile response of the ileum longitudinal smooth muscle preparation evoked by H2O2 was mainly due to the enhanced electrical activity.

Action Potentials↗
PubMed2001

Dietary supplementation of the pyridoindole antioxidant stobadine reduces vascular impairment in streptozotocin-diabetic rats.

We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on the reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month hyperglycemia were studied. Hyperglycemia was induced by streptozotocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated under isometric conditions. The first changes in aortic reactivity started after 1 month of hyperglycemia and were exhibited by significantly increased NA-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 months did not cause any additional significant changes in responsiveness to NA. Decreased ACh-induced relaxation and increased contractile responses to H2O2 were observed in month 4. The functional responses were not substantially deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic rats resulted in the protection of aortic function as well as its ultrastructure. These results suggest that abnormalities occurring in the aorta of diabetic rats might result from the damaging effects of oxygen free radicals.

Animals↗
PubMed2000

Effects of superoxide generating systems on muscle tone, cholinergic and NANC responses in cat airway.

To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.

Animals↗
PubMed2000

Extraction and chromatographic separation methods in pharmacokinetic studies of Stobadine--an indole-related antioxidant and free-radical scavenger.

This overview provides comprehensive information on the most relevant results of Stobadine preclinical disposition studies. In order to investigate pharmacokinetic processes of the drug in rats, dogs and in human volunteers, several bioanalytical assays based on radiometric, spectrofluorometric, as well as chromatographic determination methods were developed and implemented. In small laboratory animals, the drug absorption, distribution, metabolism and elimination were investigated by administering 3H-labeled Stobadine. Spectrofluorometry was used alternatively for the determination of cold/unlabeled Stobadine in extracts of biomaterials sampled from larger animal species. The chromatographic separation methods proved, however, to be the most advantageous for determining details of the drug disposition and fate in the body.

Animals↗
PubMed2000

Effect of N-acetylcysteine on colitis induced by acetic acid in rats.

(1) To verify the proposed role of reactive oxygen species (ROS) in ulcerative colitis, the effect of an antioxidant N-acetylcysteine (NAC) was studied in acetic acid (AA)-induced colonic inflammation. (2) Depending on the dose used, NAC administered intracolonically was found to reduce the extent of colonic damage, along with a decrease in myeloperoxidase (MPO) activity, colonic wet weight and wet/dry weight ratio. (3) NAC attenuated the enhanced vascular permeability and prevented the depletion of colonic reduced glutathione (GSH) caused by AA administration. (4) The findings indicate that NAC may prove beneficial in the treatment of colitis.

Acetic Acid↗
PubMed2000

[Non-selective cationic current--the basis of depolarization in smooth muscle].

The activation of smooth muscle muscarinic receptors leads to its contraction. Electrophysiological and biochemical methods have gradually, over the time span of roughly 30-40 past years, helped to reveal this phenomenon's underlying processes. One element of this cascade of processes is the influx of cations into the smooth muscle cell--non-selective cationic current--causing depolarisation of the cell membrane and subsequent opening of voltage-operated calcium channels. This mini-review provides the reader with up-to-date knowledge on non-selective cationic current, supplemented with information on muscarinic receptors of smooth muscle, their coupling with effectors via G proteins, as well as on muscarinic modulation of calcium and potassium channels of smooth muscle. The conclusion is dedicated to pointing out the future trends of research in this area. (Tab. 2, Fig. 2, Ref. 82.)

Animals↗
PubMed2000

[Morphologic and clinical sequelae of focal ischemic lesions].

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.

Adult↗
PubMed1999

Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants.

Numerous experimental data confirm the importance of reactive oxygen species (ROS) in physiological activities of smooth muscles and in the pathogenesis of various diseases with altered function of smooth muscles. The present study shows that smooth muscles of the intestine, airways and vessels, as well as their epithelium, endothelium and innervations, might be important targets of the ROS action. We demonstrated differences among the actions of various ROS (endogenous, exogenous, produced enzymatically, non-enzymatically) as well as among their actions in different smooth muscle tissues. Our results indicate that ROS are involved in changes in muscle tone, membrane conductance, calcium homeostasis, calcium-dependent processes, as well as in eicosanoid and nitric oxide metabolism. The effects of antioxidative enzymes (superoxide dismutase, catalase), of several drugs of natural origin (e.g. Kampo Medicines) and synthetic agents (e.g. stobadine, nitrosopine, ACE inhibitors) suggest that smooth muscle tissues are useful models to study ROS action and drug intervention in ROS induced injuries.

Animals↗
PubMed1999

Protective effect of stobadine in experimental colitis.

To assess the possible role of reactive oxygen species in inflammatory bowel disease, the effect of the antioxidant and free radical scavenger stobadine was studied in acetic acid-induced experimental colitis. Stobadine administered locally into the colon was found to reduce the extent of colonic mucosal injury, abolish the increase in myeloperoxidase activity, attenuate the enhanced vascular permeability, and prevent the depletion of reduced glutathione. The attempt to reduce pharmacologically excessive free radical production and oxidative damage in the inflamed colonic mucosa may be regarded as a complementary treatment of ulcerative colitis.

Acetic Acid↗
PubMed1999

Reactive oxygen species as mediators of tissue protection and injury.

Extensive research efforts during the last three decades resulted in a large body of experimental evidence that suggests an important role of the disbalance between generation and elimination of the oxygen and xenobiotic derived free radicals in physiological and pathological processes. Reactive oxygen species (ROS) are generated in many metabolic pathways, and are entering the organisms from exogenous sources, dominantly via airways and gut. ROS induced injuries, e.g. thermal, chemical, radiation, ischaemia/reperfusion, inflammation, hyperoxia, etc., result in diseases like atherosclerosis, ulcerative colitis, autoimmune diseases, asthma, etc. The current paper is designed to provide an overview of the effects ROS may exert in various tissues. Because of the effective defense systems, the tolerance of viable human cells to ROS is relatively high. The oxidant stress induced dysfunction of various systems, such as the gut, airways, nervous, cardiovascular system, etc., involve both direct and indirect mechanisms. Understanding of these molecular mechanisms is essential for a rational antioxidant therapy.

Animals↗
PubMed1998

Gastric transmucosal potential difference: effect of antisecretory and gastroprotective drugs.

1. Ion transport and electrical resistance of the gastric mucosa are responsible for the generation of the transmucosal potential difference (PD), which is considered an index of mucosal integrity. 2. The aim of the present work was to study the effect of some antisecretory and gastroprotective agents on PD in stomachs damaged by ethanol. 3. Control PD values measured in anesthetized rats were 35 to 40 mV (mucosa negative). Oral administration of 96% ethanol or intragastric instillation of 20% ethanol induced an abrupt fall in PD from the basal values of 40.4+/-1.0 mV and 39.6+/-0.1 mV to 14.6+/-2.5 mV and 11.7+/-1.3 mV, respectively. 4. Oral and/or topical pretreatment with the antisecretory agents ranitidine and timoprazole, as well as with the gastroprotective agents PGE2 and pentacaine, but not with an aluminum- and magnesium-containing antacid and with sucralfate, reduced the maximal drop of PD caused by ethanol. 5. After the administration of concentrated ethanol, hemorrhagic lesions were formed in the glandular stomach. 6. With the exception of ranitidine, all the drugs tested prevented the development of lesions after ethanol administration. 7. The results indicate that the gastric barrier can be protected by various drugs that act through different mechanisms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Hypoxia-induced inhibition of calcium channels in guinea-pig taenia caeci smooth muscle cells.

1. The effects of hypoxia on whole-cell current in single smooth muscle cells and on a high K(+)-induced contraction of strips of the guinea-pig taenia caeci were studied. 2. In physiological salt solution (PSS) and K(+)-based pipette solution, hypoxia (PO2 = 20 mmHg) reversibly inhibited both the inward Ca2+ current (ICa) and outward Ca(2+)-activated K+ current (IK(Ca)) components of the whole-cell current. 3. In PSS and Cs(+)-based pipette solution, hypoxia reversibly suppressed ICa by 30 +/- 5% at 0 mV. 4. When Ba2+ was used as a charge carrier, the IBa was suppressed by hypoxia in a potential-dependent manner, with the maximum of 40 +/- 7% at +10 mV. Alterations of concentrations of EGTA, GDB beta S or ATP in the pipette solution did not change the inhibitory effects of hypoxia on ICa and IBa. 5. In PSS with 2 mM CaCl2 replaced by CoCl2, hypoxia did not affect the Ca2+ influx-independent potassium current. 6. In cells voltage clamped at -20 mV hypoxia reversibly inhibited the spontaneous transient outward currents. 7. The response of high K(+)-contracted taenia caeci to hypoxia was composed of an initial rapid relaxation followed by a small transient contraction and slow relaxation. The transient contraction was blocked by atropine (1-10 microM), while relaxations were unaffected by atropine and guanethidine (10 microM). 8. The results show that hypoxia reversibly inhibits ICa and secondarily suppresses IK(Ca) due to decreased Ca2+ influx through Ca2+ channels. 9. It is suggested that inhibition of ICa was responsible for the rapid relaxation, whereas transient contraction may have been due to release of acetylcholine from nerve terminals upon hypoxia.

Adenosine Triphosphate↗
PubMed1997

Hydrogen peroxide induced responses of cat tracheal smooth muscle cells.

1. The effects of hydrogen peroxide (H2O2) (10(-6)-10(-3) M) on membrane potential, membrane currents, intracellular calcium concentration, resting muscle tone and contractions elicited by electrical field stimulation (EFS) and carbachol were examined in cat tracheal strips and isolated smooth muscle cells. 2. H2O2 (10(-4) and 10(-5) M) enhanced the amplitude of contractions and excitatory junction potentials (e.j.p.) evoked by EFS without changing muscle tone and resting membrane potential of the tracheal smooth muscle, and enhanced the contraction induced by carbachol (10(-3) M). At an increased concentration (10(-3) M), H2O2 elevated resting muscle tone and marginally hyperpolarized the membrane in the majority of the cells. 3. In 51 out of 56 cells examined, H2O2 (10(-6)-10(-3) M) elicited an outward current at a holding potential of -40 mV and enhanced the frequency of the spontaneous transient outward current (STOC). In 20 cells the outward current was preceded by a small inward current. In the other cells, H2O2 elicited only an inward current or did not affect the background current. 4. In Ca2+ free solution the action of H2O2 on the resting muscle tone, STOCs, background current and on the current induced by ramp depolarization was significantly reduced. 5. H2O2 (10(-4) M) increased the intracellular ionized calcium concentration both in the absence and presence of external Ca2+. However, the effect developed faster and was of a higher amplitude in the presence of external Ca2+. 6. These results suggest that H2O2 increases intracellular Ca2+, with a subsequent augmentation of stimulation-evoked contractions, and enhances Ca2+ and voltage-sensitive potassium conductance.

Animals↗
PubMed1996

Effect of pentacaine and its derivatives on the contractile responses of smooth muscle in the guinea-pig stomach.

The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic acid] and some of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyclopentyl ester of 3(n)-pentyloxyphenyl-carbanilic acid], K-2002 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], K-2006 [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], and carbanilates P2 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4-methoxy-carbonylphenyl-carbanilic acid], P3 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 3-methoxy-phenyl-carbanilic acid], and PeJ, the quaternized derivative of pentacaine), as well as that of oxethazaine was studied on longitudinal antral and circular fundic smooth muscle strips of the guinea-pig stomach. All the carbanilates studied relaxed the smooth muscle, attenuated the spontaneous smooth muscle contractions and shifted the acetylcholine, histamine, and BaCl2 cumulative concentration effect curves to the right, reducing their maximum. There was no direct relationship between their relaxing potency and the ability to reduce the action of different stimulants. For the effectiveness of the carbanilates studied, substitution in the lipophilic part of the molecule was more important than in the hydrophilic part and the meta position was more advantageous than the para position. Pentyloxy-derivatives (pentacaine, K-1905, K-2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy (P3)-derivatives. Opening of the heterocyclic ring (K-1905) in the hydrophilic part of the molecule did not affect significantly the potency of the derivative studied, while quaternization (PeJ) significantly reduced the potency. It is suggested that the carbanilates studied may affect the smooth muscle responses via changes in the membrane fluidity and Ca2+ availability, and that these effects might be partly responsible also for their antiulcer activity.

Acetylcholine↗