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Results for “Isonipecotic Acids”

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At least 19 recordsLinked to original sources
PubMed1978

Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia.

The GABA-mimetic activities of 4 analogues muscimol, isonipecotic acid, isoguvacine and N-methyl isoguvacine have been examined at the GABA receptor in the rat isolated superior cervical ganglion. The depolarizing action of all 4 analogues could be selectively antagonized by bicuculline methochloride and isopropyl bicyclophosphate. Muscimol was the only analogue more potent than GABA (molar potency ratio = 5.08 +/- 0.707). The potency of isoguvacine was 0.23 +/- 0.026 and isonipecotic acid 0.011 +/- 0.0028. N-methyl isoguvacine was less than 0.001 GABA.

Animals↗
PubMed1976

[Diphenoxinhydrochloride, a new anti-diarrhea agent].

The new antidiarrheal drug difenoxin hydrochloride is a preparation with a broad range of action; it is suitable for symptomatic treatment of acute and chronic diarrhea of varying etiology and may be administered as additional medication in cases of specific intestinal infections accompanied by diarrhea. Difenoxin hydrochloride was tested in two studies involving 220 patients with acute diarrhea and 41 patients with chronic diarrhea respectively. Side effects were extremely rare and stool frequency and consistency returned to normal at a daily dose of about 6 tablets. This dose could be reduced for the chronic cases after initial treatment with the higher dose. Positive results were obtained within a very short time in more than 80% of the acute cases and in more than 70% of the chronic cases.

Acute Disease↗
PubMed1975

Radioimmunoassay for anileridine, meperidine and other N-substituted phenylpiperidine carboxylic acid esters.

Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50% inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10(4), major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.

Animals↗
PubMed1976

[Anesthesia using piritramide and chlorpromazine in dogs].

Piritramide with chlorpromazine in doses of 3 mg kg-1 of live weight causes total anesthesia the intensity of which differs according to the breed and condition of the individual. Anesthesia sets in in 30 to 45 minutes and lasts for 3/4 to 1 1/2 hour. During the anesthesia somatic temperature and frequency of pulse decrease, and even after 24 hours they do not reach the original values. In a majority of cases breathing frequency rises insignificantly, and after 2 to 3 hours it returns to the normal. In single cases there occurs an extreme increase of the number of respirations. The per minute breath volume in the various cases and measurings differs considerably. In the course of anesthesia there occurs an increase of glucose, a decrease of the total protein, an increase of the activity of GPT and GOT, a decrease of the numbers of erythrocytes, of haematocrit and haemoglobin, an increase of pCO2 of the blood, and a decrease of the actual pH of the blood. In the number of leucocytes no changes occurred. The changes in the BE were insignificant. All deviations, except the deviations of the pulse and of the temperature, return to the original values within 24 hours. In the ECG there occurred a fluctuation in the forming of emotions and changes of the amplitude values of the QRS group and of the T wave. In the EEG striking periodical complexes of slow waves were found or combinations of slow and rapid frequencies.

Acid-Base Equilibrium↗
PubMed1977

Carcinogenesis tests of nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine in rats.

Four nitrosamines; nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine, closely related in structure to potent carcinogens, were fed chronically to rats in drinking water for one year. No toxic effects leading to life shortening were observed. There was no significant incidence of any malignant tumor other than the endocrine tumors normally found in untreated animals of our colony. This indicated that the small changes in structure represented by these compounds were sufficient to reduce greatly, or eliminate, the carcinogenic action.

Adrenal Gland Neoplasms↗
PubMed1976

[On the mode of action of difenoxin (R 15 403). Part 2: Studies on the perfused isolated colonic loop of the rat (author's transl)].

The effect of 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotinic acid hydrochloride (difenoxin, R 15 403), a new antidiarrhoic agent, was studied in vivo in rats with an isolated colonic loop. Difenoxin had no effect on transport or absorption of fluid during perfusion experiments. When given i.p. it inhibited the motility of the coecum but not that of the colon. Difenoxin has apparently no effect on normal rat colon, although an effect may have been masked by the wide variation of parameters measured under identical conditions.

Animals↗
PubMed1975

An X-ray study on the acute action of diphenoxylate on the intestinal motility in volunteers.

The intestinal inhibitory activity of 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidine-carboxylic acid ethyl ester (diphenoxylate) after a single oral dose of 5 mg was studied in 10 volunteers with X-ray diagnostic methods. The diphenoxylate treatment lengthened the transit time of the barium sulphate to caecum from 3.2 to 4.3 h. The X-ray cinematography showed the slower duodenal emptying in 5/10 of the subjects, but only in 1 of these the velocity of the peristaltic wave was clearly decreased. The results demonstrate directly the acute inhibitory action of diphenoxylate on intestinal motility with the dose used generally 3--4 times daily for the symptomatic treatment of diarrhoea.

Adult↗
PubMed1977

Radioimmunoassay for normeperidine: studies on the N-dealkylation of meperidine and anileridine.

A sensitive and specific radioimmunoassay for normeperidine has been developed that can detect as little as 100 pg of this metabolite. In competitive binding experiments with [125I]O-tyramyl-normeperidinic acid and an antiserum produced in rabbits immunized with a bovine serum albumin-normeperidinic acid conjugate, meperidine is only 0.01% as effective an inhibitor as normeperidine. Therefore, normeperidine can be determined in physiological fluids and in tissue extracts when relatively large amounts of meperidine or other N-phenylpiperidine esters are present. High pressure liquid chromatography can be used to confirm the results obtained by radioimmunoassay during the in vitro N-dealkylations of meperidine and anileridine to normeperidine. The normeperidine isolated by high pressure liquid chromatography accounts for all of the inhibitory reactivity determined in the enzymatic digests by the radioimmunoassay. Kinetic parameters (Km and Vmax) can be determined for the N-dealkylation of meperidine and anileridine. The formation of normeperidine with time can be followed in rabbits injected with meperidine or anileridine. Plasma levels may also be determined when meperidine is administered as an obsteric analgesic.

Animals↗
PubMed1975

In vitro adsorption of diphenoxylate hydrochloride on activated charcoal and its relationship to pharmacological effects of drug in vivo. I.

The adsorption of diphenoxylate hydrochloride, a potent antidiarrheal agent, on activated charcoal powder was studied in vitro. Langmuir adsorption isotherms were established at pH 4 and 7, and the maximum adsorption capacity of charcoal for this drug was estimated using these values. Activated charcoal modified the bioavailability of diphenoxylate hydrochloride in vivo. The antipropulsive action of diphenoxylate in the mouse was strongly inhibited in the presence of activated charcoal. A comparative evaluation of charcoal and chromium oxide used as inert, nonabsorbable markers revealed that chromium oxide may be the marker of choic in GI transit studies in laboratory animals since it does not influence the bioavailability of diphenoxylate hydrochloride.

Adsorption↗
PubMed1977

Determination of diphenoxylate hydrochloride and atropine sulfate in solutions and tablets.

Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbersome and, in the case of solutions, inaccurate due to spectral interferences; the proposed methods offer substantial improvements in sensitivity, specificity, and speed. Results obtained by the USP and proposed methods are compared for several lots of commercial products. The accuracy and precision of the proposed methods are shown by standard recovery studies.

Atropine↗
PubMed1976

Intracranial self-stimulation in rats as a function of various stimulus parameters. VI. Influence of fentanyl, piritramide, and morphine on medial forebrain bundle stimulation with monopolar electrodes.

The effects of different subcutaneous doses of fentanyl (0.02, 0.04, 0.08, and 0.16 mg/kg), piritramide (0.63, 2.50, 10.0 and 40.0 mg/kg), and morphine (2.50, 5.00, 10.0 and 20.0 mg/kg) on self-stimulation in rats were studied. Different stimulus parameter combinations (SPC) inducing low, high or intermediate control response rates (CRR) were applied during the same experimental sessions. The three narcotic analgesics induced response depression (RD) and response stimulation (RS). RS was mostly observed at low dose levels; RD was dose-related. SPC's inducing low CRR were more sensitive than those inducing high CRR. Fentanyl was more potent than piritramide and than morphine. The RD is related to motor incapacitation, as the doses needed to effectively reduce self-stimulation also induced obvious catatonia. The RS probably is a more specific effect reflecting sensitization of structures involved in reinforcement of behavior.

Analgesics, Opioid↗
PubMed1978

Toward the development of a potent, nonsedating, oral analgesic.

The separate and combined analgesic effects of 10 mg of oral amphetamine sulfate and 25 mg of oral anileridine dihydrochloride were studied in 24 healthy, adult, male volunteers. Tolerance of progressively increasing pain produced by the Submaximum Effort Tourniquet Technique was tested four times in each subject: after amphetamine, after anileridine, after the combination, and after a matching placebo. Treatments were administered double blind and in counterbalanced order. Elapsed time to report of slight, moderately distressing, very distressing, and unbearable pain was recorded on each trial. The four oral treatments differed significantly for very distressing and for unbearable pain. At each of the three upper pain levels, the mean tolerance times for anileridine and amphetamine were similar; each was longer than placebo but shorter than the combination; and the effect of the combination was approximately the sum of the effects of the two components.

Administration, Oral↗
PubMed1977

Effect of antidiarrheal and antimotility drugs on ileal excreta.

Commonly used antimotility and antidiarrheal drugs were administered to six ileostomized subjects to determine whether their normal ileal excreta and that induced by prune juice could be altered. A total of 49 studies were performed, 21 with and 28 without prune juice. Bismuth subgallate was the only drug which significantly reduced the normal ileal excreta (P less than 0.05). Codeine sulfate decreased the ileal excreta in two of three subjects in either type of study. The third subject was a nonresponder to drugs. Deodorized tincture of opium (DTO) and diphenoxylate (Lomotil) were also effective in some subjects. Propantheline, tincture of belladonna, Sorboquel, and Kaopectate did not appear to decrease ileal excreta. Calcium carbonate, on the other hand, increased ileal excreta; fat excretion was also increased.

Adult↗