Neuromuscular electrical stimulation as an adjunctive therapy to drotaverine hydrochloride for treating patients with diarrhea-predominant irritable bowel syndrome: A retrospective study.

This retrospective study investigated the effectiveness and safety of neuromuscular electrical stimulation (NMES) as an adjunctive therapy to drotaverine hydrochloride (DHC) in patients with diarrhea-predominant irritable bowel syndrome (BP-IBS).A total of 108 patient cases with BP-IBS were included in this study. Of these, 54 cases were assigned to a treatment group and received NMES and DHC, whereas the other 54 subjects were assigned to a control group and underwent DHC alone. All patients were treated for a total of 4 weeks. Primary outcomes were measured by the visual analog scale (VAS), and average weekly stool frequency. Secondary outcome was measured by the Bristol scale. In addition, adverse events were documented. All outcome measurements were analyzed before and after 4-week treatment.Patients in the treatment group did not show better effectiveness in VAS (P = .14), and average weekly stool frequency (P = .42), as well as the Bristol scale (P = .71), compared with the patients in the control group. Moreover, no significant differences in adverse events were found between 2 groups.The results of this study showed that NMES as an adjunctive therapy to DHC may be not efficacious for patients with BP-IBS after 4-week treatment.

[Nutricional support in the complex treatment of a patient with esophageal spasm].

In the presented clinical case the theme of the need for an integrated therapeutic intervention has been disclosed, including nutritional support on the various links of the pathogenesis of esophagospasm to the effectiveness of the patient's treatment.

Interactions between symptoms and motor and visceral sensory responses of irritable bowel syndrome patients to spasmolytics (antispasmodics).

AIM: to evaluate and correlate the symptomatic, motor and sensory responses to two widely used categories of spasmolytic agents in irritable bowel syndrome (IBS). METHODS: 118 patients with IBS, diagnosed by Rome II criteria and 45 healthy individuals were studied. In the IBS subjects, pain severity, as well as the sensory response to rectal balloon distention and rectal and sigmoid motility, were studied at baseline and after two weeks therapy with either oral buscopan (20 mg three times a day, n=37), a buscopan suppository (30 mg once daily, n=21), oral drotaverine (80 mg three times a day, n=30), calcium gluconate tablets (one three times a day, n=16) as a control for oral agents, or calendula suppository (once daily, n=14) as a control for those who received a suppository. RESULTS: Buscopan, whether administered as a tablet or a suppository, produced a significant reduction in pain scores among IBS patients with predominant diarrhea. No significant differences were evident among other IBS subgroups or in response to drotaverine. None of the interventions had any effect on any of the parameters of rectal or sigmoid motility studied. However, both buscopan and drotaverine led to a significant augmentation of the rectal threshold for discomfort/pain among IBS subjects with predominant diarrhea [21.78 + or - 2.8 vs 39.60 + or - 2.4 (p<0.05), 20.5 + or - 2,8 vs 36.84 + or - 3.8 (p<0.05) and 22.18 + or - 2.8 vs 36.9 + or - 2.42 (p<0.05) for oral buscopan, rectal buscopan and oral drotaverine, respectively]. CONCLUSION: We conclude that the clinical benefits of supposed spasmolytic (anti-spasmodic) agents may relate more to effects on visceral sensation than motility.

The significance of putative urinary markers of illicit heroin use after consumption of poppy seed products.

After consumption of poppy seeds various substances were detected in urine or blood samples using an immunoassay and a sophisticated liquid chromatographic-tandem mass spectrometric procedure. These compounds are widely considered to be putative markers of heroin (HER) abuse whereas acetylcodeine was regarded as a marker for illicit preparations ("street HER"). Besides positive urinary opiate immunoassay results during a 48 hours monitoring period, peak concentrations of morphine (MOR), codeine and their glucuronides appeared 4 to 8 hours after ingestion of poppy seeds, and concentrations of total MOR higher than 10 microg/mL were observed. Also, in serum samples taken up to 6 hours after consumption, MOR glucuronides were found. Free MOR was only detected in traces (1 to 3 ng/mL) within 2 hours of consumption. In addition, 3 of 6 onsite opiate sweat tests revealed positive results 6.5 hours after ingestion. Furthermore, it was demonstrated that neither noscapine (NOS) nor papaverine (PAP) was detectable in urine or blood samples after the consumption of poppy seeds containing up to 94 microg NOS and up to 3.3 mug PAP. NOS and PAP were rapidly metabolized, whereas desmethylpapaverine and, especially, its glucuronide were found in urine samples of poppy seed consumers even 48 hours after consumption. According to these results PAP metabolites should not be regarded as markers of illicit HER abuse. In conclusion, only acetylcodeine can be regarded as a specific marker but has the problem of a short half-life. Therefore, we suggest that NOS and PAP, but not their metabolites, might be used cautiously as additional markers of illicit HER abuse as they have not been detected after oral intake of poppy seeds in normal doses. But it must be kept in mind that in some cases poppy seeds with an unusually high content of these alkaloids could be available, and that these substances are also agents in some pharmaceuticals.

[The characteristics of the analgesic action of nitrosorbide and no-shpa]. / Kharakteristika obezbolivaiushchego deistviia nirtosorbida i no shpy.

The study was conducted on experimental models of pain sense induced in mice by exposure to thermic or chemical factors and in rats by exposure to electric factors. Nitrosorbide and no-spa possess a dose-dependent analgesic effect. Both drugs excelled analgin in the intensity and duration of analgesic effect.

[The anti-edematous effect of the preparation polyosm in acute hypertensive encephalopathy]. / Protivootechnyi éffekt preparata poliosm pri ostroi gipertonicheskoi éntsefalopatii.

Experiments were conducted on Wistar rats to study the effect of intravenous infusion of polyosm (solution of polyethyleneoxide 400) on the parameters of brain tissue edema-swelling (according to impedancemetry findings) and the local cerebral blood flow on a model of acute hypertensive encephalopathy. Under such conditions the drug hastened involution of edema-swelling of the brain tissue and prevented a decrease in cerebral blood flow.

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Antispasmodic activity of benzylisoquinoline alkaloids analogous to papaverine.

In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both.

Comparative studies of drotaverine--acephyllinate (Depogen) and pentoxifylline (Trental).

Pentoxifylline is an orally active agent for the treatment of peripherial and cerebral vascular diseases. Pentoxifylline increases the deformability of red blood cells in vitro, reduces blood viscosity and decreases platelet aggregation and thrombus formation. Depogen has shown antiaggregatory effect both in vitro and in ex vivo. The inhibitory effect of Pentoxifylline was about 3-5 times weaker than that of Depogen. IC50 = 900/micrograms/ml for Depogén and 3600/micrograms/ml for Pentoxifylline on human platelet rich plasma. Depogen has shown ex vivo antiaggregatory effect on anesthetised rabbits, ID50 = 7 mg/kg in case of iv. administration, and ID50 = 300 mg/kg in case of orally administration. Both compound inhibit the release of platelet precoagulation factor, but the effect of Pentoxifylline was slighter.

[Effect of komplamin and nikoshpan on brain circulation and metabolism in the postischemic period]. / Vliianie komplamina i nikoshpana na krovoobrashchenie i metabolizm golovnogo mozga v postishemicheskom periode.

Intravenous administration of komplamin to anesthetized cats before the brain ischemia or in the early period following ischemia prevents the development of the postischemic phenomenon of the cerebral blood flow nonrecovery and beneficially influences the cerebral metabolism: restores oxygen and glucose consumption by the brain, decreases pyruvic acid level in the arterial and venous blood, attenuates the phenomenon of acidosis. Nikoshpan improves the blood supply to the brain, restores oxygen and glucose consumption by the brain in the postischemic period only if administered before the brain ischemia.

[Effect of euphylline and no-shpa on cerebrovascular resistance and the survivability of animals after cerebral ischemia]. / Vliianie éufillina i no-shpy na tserebrovaskuliarnoe soprotivlenie i vyzhivaemost' zhivotnykh posle ishemii golovnogo mozga.

In acute experiments on anesthetized cats with total ischemia of the brain (15-minute arrest of blood autoperfusion of the cerebral vessels by a stable blood volume) it was shown that euphylline and no-shpa administered before ischemia or in the early period after ischemia inhibit or prevent the development of the postischemic phenomenon of non-recovery of the cerebral blood flow. The two drugs contributed to survival of albino rats following the brain ischemia produced by ligation of both carotid arteries.

Inhibition of catechol-O-methyltransferase by 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine: demonstration using liquid chromatography and a novel substrate for O-methylation.

We report that 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine are potent inhibitors of catechol-O-methyltransferase (COMT), but are not apparent substrates for the enzyme in vitro or in vivo. Three dihydroxy (catecholic) dihydroisoquinolines, including the 1-benzyl (DesDHP) and the 1-methyl (DSAL) analogs, were found to inhibit COMT activity in rat liver supernatant more effectively than the well-known inhibitor, tropolone. Inhibition of O-methylation was uncompetitive with substrate, and O-methylated products of the catecholic dihydroisoquinolines were undetectable. For these in vitro studies, a facile liquid chromatographic assay was developed utilizing as a site-specific substrate, 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline-1-carboxylate (salsolinol-1-carboxylate). This catechol produces only one phenolic product isomer when incubated with liver supernatant and S-adenosylmethionine. Following central injection of DSAL in rats, inhibition of brain COMT in vivo was indicated by the reduced brain levels of homovanillic acid, but not of 3,4-dihydroxyphenylacetic acid. Furthermore, O-methylated DSAL metabolites could not be detected in brain by liquid or gas chromatography. We suggest that 6,7-dihydroxy-dihydroisoquinolines are "nonmethylatable" COMT inhibitors because they exist as quinoidal tautomers resembling pyridones or tropolones rather than as catechols. Quinoid formation is supported by the fluorescence and ultraviolet spectra for DSAL and its O-methyl derivatives. The experiments reveal a new class of COMT inhibitors that may be of pharmacological and mechanistic value. Additionally, 3,4-dihydroisoquinolines could arise endogenously via oxidation of the 1,2,3,4-tetrahydroisoquinolines which are ingested or produced from cellular catecholamine condensations. However, it is unlikely that dihydroisoquinoline (e.g., DSAL) concentrations necessary to inhibit COMT significantly would be attained via endogenous pathways.

Effect of ethaverine hydrochloride on cochlear microcirculation.

The effect of ethaverine hydrochloride on cochlear microcirculation was observed in short-term experiments on 11 guinea pigs. In these experiments, the endocochlear PO2, endocochlear potential (EP), cochlear microphonic (CM) potential, and blood pressure (BP) were recorded. Endocochlear PO2 was measured polarographically by gold electrodes in the scala media. Ethaverine hydrochloride was administered by intravenous infusion for ten minutes in doses of 2, 5, and 10 mg/kg. These experiments demonstrated that ethaverine hydrochloride in doses of 5 and 10 mg/kg caused significant elevation of endocochlear PO2 for 35 to 90 minutes, even when the BP temporarily declined. At the same time, it was observed that this improvement of cochlear microcirculation coincided with an increase of the CM potential. Decrease of the EP is probably the result of BP decline and a direct action of ethaverine on EP generation.

Biosynthesis of unnatural papaverine derivatives in Papaver somniferum.

The unnatural thebaine analog, oripavine 3-ethyl ether, was efficiently metabolized to morphine 3-ethyl ether and morphine in the opium poppy. An attempt to detect oripavine hy an isotope dilution experiment based on its presumed biosynthesis from reticuline was unsuccessful.

Screening pharmacological studies of four dihydroisoquinoline derivatives.

Screening studies are carried out of the pharmacological activity of 3,4-dihydropapaverine (DHP) and three of its newly-synthesized derivatives: 6'-iodo-DHP, 6'-bromo-DHP and 6'-iodu-DHP methiodide. All compounds studied manifest central depressive action which is manifested in general depression, potentiation of hexobarbital anaesthesia, without inducing sleep when independently applied, as well as inhibition of the spontaneous and amphetamine-induced motor activity of mice. 6'-Iodo-DHP and its methiodide manifest analgesic effect. All four compounds studied reduce the blood pressure of urethane-anaesthesized cats, but they do not change the noradrenaline and the acetylcholine effects. The hypotensive effect of the compounds is preserved even after atropinization of the cats. The compounds studied manifest no antitussive effect. DHP-derivatives eliminate the spasms in guinea-pig colon, induced by BaCl2 and nicotine, while DHP has no effect on them. 6'-Iodo-DHP methoiodide inhibits the hypertensive nicotine effect on cats. DHP and 6'-iodo-DHP methoiodide manifest vasoconstricting action upon perfusion of the blood vessels of isolated rat hind legs.