piperidines and Spasm

Topics: Adult; Benzilates; Benzoates; Colonic Diseases, Functional; Cyclohexanecarboxylic Acids; Cyclohexanes; Diarrhea; Diethylamines; Female; Gastrointestinal Motility; Humans; Male; Middle Aged; Parasympatholytics; Phenethylamines; Piperidines; Scopolamine; Scopolamine Derivatives; Spasm; Syndrome

Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer's tolerate donepezil better than patients with MCI.

Topics: Adult; Aged; Aged, 80 and over; Amnesia; Cholinesterase Inhibitors; Cognition Disorders; Diarrhea; Donepezil; Double-Blind Method; Female; Follow-Up Studies; Humans; Indans; Male; Middle Aged; Nausea; Neuropsychological Tests; Piperidines; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Spasm; Time Factors; Treatment Outcome

A prospective, randomized, double-blind study was undertaken to evaluate Zamifenacin 30 mg (Pfizer Ltd), a novel, orally-administered, gut-specific muscarinic receptor antagonist, as an adjuvant to the double contrast barium enema examination (DCBE). Zamifenacin was compared with placebo in terms of side-effects and colonic tone. Analysis of colonic tone was carried out by two independent observers, using a subjective grading system and also by an objective method using computerized planimetry. Interobserver variability was also assessed. Zamifenacin is safe and well tolerated but at the prescribed dose is an ineffective antispasmodic for DCBE. Subjective assessment of colonic tone was shown to be of limited value whilst the objective analysis using computerized planimetry was reliable and highly reproducible.

Topics: Adolescent; Adult; Aged; Barium Sulfate; Colon; Colonic Diseases; Dioxoles; Double-Blind Method; Enema; Humans; Image Processing, Computer-Assisted; Middle Aged; Muscarinic Antagonists; Observer Variation; Piperidines; Prospective Studies; Radiography; Spasm

Topics: Adult; Animals; Colic; Dioxolanes; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Kidney Calculi; Male; Pain; Parasympatholytics; Piperidines; Rats; Spasm; Suppositories; Time Factors

Opioids cause spasm of the sphincter of Oddi. Remifentanil is metabolized enzymatically throughout the body. Its context-sensitive half-time is 3 to 4minutes. The effect of remifentanil on the sphincter of Oddi is unknown, especially in children. We recently encountered a patient in whom the administration of remifentanil caused spasm of the sphincter of Oddi, which resolved rapidly after discontinuation of remifentanil. A 3-year-old girl weighing 11.3kg was scheduled to undergo common bile duct excision with ductoplasty. Her diagnosis was congenital biliary dilatation. In the operating room, after achieving the initial induction through sevoflurane (5%) and intravenous rocuronium (10mg), she was intubated and administered a continuous paravertebral block by levobupivacaine (25mg/10mL +2.5mg/h). General anesthesia was maintained with sevoflurane (2%), remifentanil (0.5 μg kg(-1) min(-1)), and oxygen (fractional inspired oxygen tension, 0.33). The first intraoperative cholangiogram obtained via the cystic duct tube showed obstruction at the terminal end of the common bile duct. We injected scopolamine butylbromide (5mg, intravenous) to relax the sphincter of Oddi. However, the next cholangiogram obtained 3minutes later still showed an obstruction. We speculated that the obstruction may have been caused by remifentanil-induced spasm of the sphincter of Oddi. Therefore, we stopped administering remifentanil; 2minutes later, we achieved satisfactory passage of the contrast material to the duodenum. The predicted plasma concentrations of remifentanil at the time of stopping its administration and at the time of disobliteration were 6.38and 2.55ng/mL, respectively. The patient's postoperative course was uneventful. In patients who have spasms of the sphincter of Oddi during the administration of remifentanil, the resultant obstruction can be treated effectively by reducing the infusion rate of remifentanil.

Topics: Analgesics, Opioid; Child, Preschool; Female; Humans; Piperidines; Remifentanil; Spasm; Sphincter of Oddi

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Agenesis of Corpus Callosum; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Anticonvulsants; Child; Eye Diseases, Hereditary; Female; Glycopyrrolate; Humans; Intellectual Disability; Laryngoscopy; Midazolam; Nitrous Oxide; Oral Surgical Procedures; Piperidines; Remifentanil; Spasm; Syndrome

Biliary, ureteric and intestinal colic are extremely common clinical conditions associated with smooth muscle spasm. In the present study, antispasmodic activity was carried out against acetylcholine (10-640 ng/ml)-induced contractions on guinea pig ileum. Acetylcholine (10-640 ng/ml) induced concentration-dependent contraction of smooth muscle. Diclofenac, in varying concentration (9.4 x 10(-5) mol/l and 14.1 x 10(-5) mol/l) shifted the concentration response curve of acetylcholine to the right without suppressing the maximal response. However, in higher concentration diclofenac (18.9 x 10(-5) mol/l) blocked the response in an unsurmountable fashion. Further, analgin (11.09 x 10(-5), 16.63 x 10(-5) and 22.18 x 10(-5) mol/l) in equimolar concentrations did not alter the concentration response curve of acetylcholine, but in higher concentration analgin (44.36 x 10(-5) mol/l) also blocked the response in an unsurmountable fashion. Pitofenone (2.5 x 10(-6) mol/l) also, shifted the concentration response curve of acetylcholine to right in a parallel fashion with no change in maximal response. The present study confirms the potent antispasmodic activity of diclofenac-pitofenone combination in comparison to analgin-pitofenone in molar equivalent concentration (in comparison to diclofenac) against acetylcholine-induced contractions of guinea pig ileum.

Topics: Acetylcholine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzophenones; Cholinergic Agents; Diclofenac; Dipyrone; Dose-Response Relationship, Drug; Female; Guinea Pigs; Ileum; Male; Muscle Contraction; Muscle, Smooth; Parasympatholytics; Piperidines; Spasm

Spasticity is a complicating sign in multiple sclerosis that also develops in a model of chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice. In areas associated with nerve damage, increased levels of the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG), and of the AEA congener, palmitoylethanolamide (PEA), were detected here, whereas comparable levels of these compounds were found in normal and non-spastic CREAE mice. While exogenously administered endocannabinoids and PEA ameliorate spasticity, selective inhibitors of endocannabinoid re-uptake and hydrolysis-probably through the enhancement of endogenous levels of AEA, and, possibly, 2-arachidonoyl glycerol-significantly ameliorated spasticity to an extent comparable with that observed previously with potent cannabinoid receptor agonists. These studies provide definitive evidence for the tonic control of spasticity by the endocannabinoid system and open new horizons to therapy of multiple sclerosis, and other neuromuscular diseases, based on agents modulating endocannabinoid levels and action, which exhibit little psychotropic activity.

Topics: Amides; Animals; Arachidonic Acids; Brain; Cannabinoid Receptor Modulators; Cannabinoids; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Endocannabinoids; Ethanolamines; Glycerides; Humans; Mice; Mice, Inbred Strains; Multiple Sclerosis; Palmitic Acids; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Spasm; Spinal Cord

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, delta9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis, and provides a means of evaluating more selective cannabinoids in the future.

Topics: Animals; Camphanes; Cannabinoids; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Mice; Multiple Sclerosis; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Spasm; Tremor

The tachykinin NK1 receptor agonist substance P methyl ester (SPOME) impedes intestinal peristalsis by releasing nitric oxide (NO) from inhibitory motor neurones. Since NK1 receptor agonists differ in their receptor interaction, we set out to compare a range of NK1 receptor agonists including SPOME, septide and GR-73 632 in their effects on propulsive peristalsis and circular muscle activity in the guinea-pig isolated small intestine. SPOME (100-300 nM) inhibited peristalsis by a rise of the pressure threshold at which peristaltic waves were triggered, whereas septide and GR-73 632 (30-300 nM) interrupted peristalsis by causing circular muscle spasms. Separate experiments showed that all three NK1 receptor agonists caused contraction of the circular muscle, which was enhanced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (300 mM) and the P2X purinoceptor antagonist suramin (300 mM). In contrast, tetrodotoxin (300 nM) augmented the contractile effect of septide and GR-73 632 but not that of SPOME. It is concluded that the motor response to NK1 receptor agonists involves release of NO and adenosine triphosphate from inhibitory motor neurones. However, the NK1 receptor agonists differ in the mechanism by which they cause inhibitory transmitter release, which corresponds to differences in their antiperistaltic action.

Topics: Adenosine Triphosphate; Animals; Enzyme Inhibitors; Female; Guinea Pigs; Intestine, Small; Male; Motor Neurons; Muscle Contraction; Muscle, Smooth; Neurokinin A; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Peptide Fragments; Peristalsis; Piperidines; Purinergic P2 Receptor Antagonists; Pyrrolidonecarboxylic Acid; Quinuclidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Sincalide; Spasm; Substance P; Suramin; Tetrodotoxin

The effects of sigma receptor ligands on the neurogenic twitch contraction in the ddY mouse vas deferens were studied. In functional studies, (+)-N-allylnormetazocine ((+)-SKF-10,047) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) potentiated neurogenic twitch contractions in a concentration-dependent manner. The potentiation by each (+) enantiomer was significantly more potent than that by the respective (-) enantiomer. In addition, haloperidol and (+/-)-pentazocine also potentiated neurogenic twitch contractions. The order of potentiating ability was: haloperidol > (+/-)-pentazocine > (+)-3-PPP > (-)-3-PPP > (+)-SKF-10,047 > (-)-SKF-10,047. In contrast, other sigma receptor ligands, 1,3-di(2-tolyl)guanidine (DTG) and rimcazole, suppressed this twitch contraction. In addition, rimcazole significantly antagonized the (+)-SKF-10,047-induced potentiation at concentrations which did not affect contractions per se. Furthermore, binding studies showed that the kinetic parameters and the inhibitory potencies of sigma receptor ligands for the binding of [3H](+)-SKF-10,047 in the mouse vas deferens were similar to those in the guinea pig brain. The order of potency of sigma receptor ligands to potentiate the neurogenic twitch contraction in the mouse vas deferens was significantly correlated with the potency to inhibit [3H](+)-SKF-10,047 binding in both mouse vas deferens and guinea pig brain. These results indicate that sigma receptor ligands regulate the neurogenic twitch contraction, which is mediated by rimcazole-sensitive benzomorphan-type sigma receptors.

Topics: Animals; Antiparkinson Agents; Brain; Drug Synergism; Guinea Pigs; Haloperidol; Ligands; Male; Mice; Phenazocine; Piperidines; Receptors, sigma; Spasm; Vas Deferens

Topics: Adult; Aged; Cellulase; Child, Preschool; Colonic Diseases, Functional; Dehydrocholic Acid; Dimethylpolysiloxanes; Drug Combinations; Glycoside Hydrolases; Humans; Middle Aged; Pancreatin; Pepsin A; Piperidines; Silicones; Spasm; Thioxanthenes

Topics: Amides; Analgesics; Animals; Cough; Dose-Response Relationship, Drug; Drug Antagonism; Drug Evaluation, Preclinical; Drug Synergism; Edema; Female; Fumarates; Hindlimb; Humans; Male; Motor Activity; Pain; Piperidines; Propionates; Pyridines; Respiration; Self Medication; Spasm; Substance Withdrawal Syndrome; Tail

Topics: Anilides; Animals; Anti-Arrhythmia Agents; Ergolines; Female; Heart Rate; In Vitro Techniques; Mice; Muscle Contraction; Piperidines; Quinidine; Rats; Serotonin Antagonists; Spasm; Structure-Activity Relationship; Uterus

Topics: Androstanes; Anesthesia, General; Animals; Fever; Injections, Intravenous; Neuromuscular Nondepolarizing Agents; Piperidines; Spasm; Swine

Topics: Adult; Aged; Asthma; Biliary Tract Diseases; Dioxoles; Drug Tolerance; Duodenal Diseases; Dysmenorrhea; Esophagitis; Female; Gastritis; Heart Diseases; Humans; Kidney Calculi; Male; Middle Aged; Migraine Disorders; Muscles; Piperidines; Spasm

Topics: Adult; Aminopyrine; Benzilates; Colic; Drug Synergism; Female; Gallbladder Diseases; Gastrointestinal Diseases; Humans; Male; Middle Aged; Muscles; Pain; Piperidines; Spasm; Urologic Diseases

Topics: Aged; Blindness; Eyelids; Humans; Hysteria; Male; Piperidines; Spasm

Topics: Antihypertensive Agents; Diet, Reducing; Epilepsy; Intellectual Disability; Methylphenidate; Muscle Spasticity; Piperidines; Reserpine; Secologanin Tryptamine Alkaloids; Spasm

Topics: Parasympatholytics; Piperidines; Spasm