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PubMed2001

Intrathecal treatment for spasticity.

Although initially to be treated by oral spasmolytics, established spasticity is being increasingly recognised as needing direct pharmacotherapy to the spinal cord by the intrathecal route using drug delivery systems. Although the spasticity is mainly of spinal origin due to trauma or multiple sclerosis (M.S.), it can emanate from the brain as in cerebral palsy in children and require the same direct treatment. Drug delivery systems are now proven to be safe, clinically reliable, and cost effective and should be considered earlier in the disease process.

Drug Delivery Systems↗

PubMed2003

Effect of butylated hydroxyanisole and some of its derivatives on human neutrophil oxidative burst: chemiluminescence evaluation.

An acute inflammatory response begins during the reperfusion phase following an ischemic insult in which polymorphonuclear neutrophils (PMNs) play an important role and the release of reactive oxygen species (ROS) causes further damage and a reduction in endogenous antioxidant storage. The ability of butylated hydroxyanisole (BHA) and some phenolic, aliphatic and aromatic BHA derivatives to reduce the human PMN oxidative burst evoked by particulate (Candida albicans and zymosan) or soluble stimulants [N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA)] was investigated using luminol-amplified chemiluminescence. BHA and the derivative dt-BHA [3,5-di-t-butyl-4-hydroxyanisole] significantly reduced the PMN oxidative burst at concentrations ranging from 5 x 10(-6) to 5 x 10(-5) mol/l for C. albicans stimulation, while for zymosan stimulation, reduction was seen at concentrations ranging from 5 x 10(-6) to 5 x 10(-5) mol/l for BHA, and at concentrations ranging from 5 x 10(-7) to 5 x 10(-5) mol/l for dt-BHA, with dt-BHA being the most active. Another BHA derivative, Bu GAM 1, was active at 5 x 10(-5) mol/l for C. albicans and at 5 x 10(-6) to 5 x 10(-5) mol/l for zymosan. The findings obtained with fMLP and PMA were very similar to those previously reported. ROS release is related to PMN killing activity, but the inhibition of the PMN oxidative burst induced by BHA and BHA derivatives did not significantly modify PMN phagocytosis or killing. It has recently been observed that dt-BHA has a spasmolytic action by inhibiting the influx of Ca(2+) into cells through L-type Ca(2+) channels, which means that a single molecule is capable of counteracting two major steps in the sequence of events triggered by ischemia-reperfusion injury, i.e. free radical release and Ca(2+) overload.

Adult↗

PubMed2003

[The common butterbur (Petasites hybridus)--portrait of a medicinal herb].

For hundreds of years butterbur (Petasites hybridus) has been used against many diseases. Modern indications are the prophylaxis of migraine, tension headache, spasms of the urogenital tract, gastro-intestinal tract and bile duct and hopefully hay fever and asthma in the near future. The petasines, the main components of butterbur, inhibit the synthesis of leucotrienes and decrease the intracellular concentration of calcium which explains the anti-inflammatory and spasmolytic properties of extracts of butterbur. Thanks to extraction with supercritical CO(2) the concentrations of the potentially hepatotoxic and carcinogenic pyrrolizidine alkaloids lie below the detection limits. Until now four cases of a reversible cholestatic hepatitis have been probably associated with long-term administration of butterbur (incidence of 1:175.000). It is unknown which components of butterbur are responsible for the long-term hepatotoxicity. Further side effects involve the gastrointestinal tract and are usually mild.

Gastrointestinal Diseases↗

PubMed2005

Management of diverticular disease: is there room for rifaximin?

Treatment of symptomatic diverticular disease of the colon is aimed at the relief of symptoms and the prevention of major complications. The efficacy of fiber supplementation and of anticholinergic and spasmolytic agents remains controversial. Antibiotics are commonly used in the treatment of inflammatory complications of diverticular disease. Data from open labelled and randomized controlled trials do suggest the efficacy of rifaximin in obtaining symptomatic relief in patients with diverticular disease. Approximately 30% therapeutic gain compared to fiber supplementation only can be expected after one year of intermittent treatment with rifaximin. Considering the safety and tolerability of rifaximin, this drug can be recommended for patients with symptomatic uncomplicated diverticular disease.

Anti-Bacterial Agents↗

PubMed2005

A simple and effective regimen for prevention of radial artery spasm during coronary catheterization.

Radial artery spasm occurs frequently during the transradial approach for coronary catheterization. Premedications with nitroglycerin and verapamil have been documented to be effective in preventing radial spasms. Verapamil is relatively contraindicated for some patients with left ventricular dysfunction, hypotension and bradycardia. We would like to know whether nitroglycerin alone is sufficient for the prevention of radial artery spasm. We conducted a randomized controlled trial to compare the spasmolytic effect between heparin alone, heparin plus nitroglycerin and heparin plus nitroglycerin and varapamil during transradial cardiac catheterization. In this study, a total of 406 patients underwent transradial cardiac catheterization and intervention. After successful cannulation and sheath insertion of radial arteries, 133 patients in group A received 3,000 units of heparin, 100 microg of nitroglycerin and 1.25 mg of verapamil via sheath, 135 patients in group B received 3,000 units of heparin and 100 microg of nitroglycerin, and 93 patients in group C received 3,000 units of heparin. Five patients in group A (3.8%), 6 patients in group B (4.4%) and 19 patients in group C (20.4%) showed radial spasms. There is no statistically significant difference between groups A and B (p = 0.804), but there are strong statistically significant differences between groups A and C (p = 0.001) and groups B and C (p = 0.003). Intra-arterial premedication with 100 microg nitroglycerin and 3,000 units of heparin is effective in preventing radial spasms during transradial cardiac catheterization.

Aged↗

PubMed2006

Airway smooth muscle relaxations induced by dipyrone.

BACKGROUND: Dipyrone differs from other nonsteroidal anti-inflammatory drugs with a distinctive spasmolytic effect; however, the mechanism of action is not clear yet. The possible mechanism behind this effect was investigated on airway smooth muscle tone in vitro. METHOD: The effect of dipyrone on inositol phosphate (IP) accumulation was evaluated on guinea pig trachea smooth muscle. Changes in intracellular free calcium levels and IP accumulation were evaluated in LTK8 cells. RESULTS: Dipyrone (0.01, 0.1, 1 mmol/l) had a relaxing effect on histamine (0.02 mmol/l)- and adenosine triphosphate- (ATP) (0.01 mol/l)-induced contractions, but not potassium chloride (KCl)-stimulated contractions. This relaxing effect was not observed with indomethacin. Indomethacin did not inhibit the relaxation response of dipyrone. In isolated tracheal smooth muscle, histamine- (0.02 mmol/l) and ATP (0.01 mmol/l)-induced IP accumulation was significantly inhibited by dipyrone (1 mmol/l). ATP (0.01 mmol/l)-induced IP accumulation was also significantly inhibited by dipyrone (0.01 mmol/l) in LTK8 cells. Dipyrone inhibited ATP-induced (0.01 and 0.1 mmol/l) intracellular calcium increase in LTK8 cells. CONCLUSION: Inhibition of the release of intracellular Ca(2+) may play a role in the smooth muscle relaxing effect of dipyrone. The inhibitor effect of dipyrone on IP accumulation may be due to direct inhibition of phospholipase C (PLC) or impairment of the activation of PLC by G protein-coupled receptor (GPCR).

Adenosine Triphosphate↗

PubMed1978

Physiopathological approach to the management of cerebral ischaemia.

Pharmacological therapy in ischemic and in microcirculatory and cerebral metabolic damage is considered. In the first case osmotic drugs and membrane stabilisers are useful, i.e., cortisone and non-steroid anti-inflammatory drugs, as well as anti-aminics and spasmolytics. Platelet anti-aggregants and increase in perfusion pressure are also useful in order to prevent the 'no-reflow' phenomenon. In the second case the theoretical possibilities of pharmacological action concern activation of glycogen synthetase and adenylcyclase or inhibition of phosphodiesterase. It will be necessary to remove the lactate increase and to raise the glucose supply, while for the oedema, osmotic and oncotic drugs will need to be used.

Anti-Inflammatory Agents↗

PubMed1987

Calcium-channel-blocking agent in the treatment of acute alcohol withdrawal--caroverine versus meprobamate in a randomized double-blind study.

We present a randomized double-blind study on the efficacy of caroverine in the treatment of alcohol withdrawal symptoms. The group B Ca2+ channel blocking agent caroverine was tested against meprobamate in inpatient treatment of alcohol withdrawal. Patients of both groups were similar in age, weight, duration of drinking, ingested quantities of alcohol and intensity of withdrawal symptoms in both groups. The symptoms were quantified daily by Syndromkurztest (SKT), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), NGI; the Webster scale was applied to rate tremor, speech and coping. Duration of study was scheduled for 5 days after which other medication, e.g., levopromazine was applied if needed. As caroverine is registered and used as a spasmolytic drug in Austria, patients' verbal consent was sufficient. In both compounds we registered no difference of clinical efficacy, though caroverine presented less sedative side effects. This may be an important factor in the treatment and management of alcohol withdrawal symptoms. Dose ranges were 120 mg/day vs. 2,400 mg/day of caroverine and meprobamate, respectively. Thus, drug loading and metabolism can be thoroughly reduced by the application of caroverine--another important point in treatment of alcoholism. In 4 cases of manifest delirium tremens the infusional application of caroverine was openly tested with dose ranges of 2.5-5.0 mg/kg (24 h). Clinical effects were estimated to be similar with oral application as was therapeutic efficacy. This novel indication of a group-B Ca2+ channel blocker presents an interesting feature, which seems to warrant further investigation.

Adult↗

PubMed1996

A third P-domain peptide gene (TFF3), human intestinal trefoil factor, maps to 21q22.3.

Small peptides displaying a cysteine-rich module (termed P-domain or trefoil motif) form a recently increasing group of peptides abundantly expressed at mucosal surfaces of specific tissues and are associated with the maintenance of surface integrity. The estrogen-inducible pS2 gene (BCEI) and the human homolog to the porcine spasmolytic peptide (hsP) gene (SML1) appear synchronously expressed in healthy stomach mucosa and several carcinomas of the gastrointestinal tract. Both genes were shown to be located at 21q22.3. A new trefoil peptide from human intestinal mucosa (hITF/hP1.B) and its gene (TFF3) were described recently. By PCR analysis of a somatic cell hybrid panel and FISH using two large genomic recombinants (110 kb, 210 kb) cloned in the Bacterial Artificial Chromosome (BAC) system, we show that this gene coding for the new member of human P-domain/trefoil peptides also maps to chromosome region 21q22.3 suggesting a physical linkage of all three trefoil peptide genes.

Amino Acid Sequence↗

PubMed1977

Characterization of the oxybutynin antagonism of drug-induced spasms in detrusor.

Oxybutynin chloride exerts a moderate anticholinergic effect on rabbit detrusor in vitro, which is reversible and competitive in nature (KB = 4.7 x 10(-9), and midway in potency between atropine and papaverine. In addition, oxybutynin strongly antagonizes BaCl2-induced spasms of detrusor with a potency equivalent to that of papaverine and 10 times that of atropine. This musculotropic spasmolytic effect is slightly greater in rabbit than human or monkey tissue, and noncompetitive (pD2 = 5.5). This direct relaxant effect, unlike that of papaverine, is not mediated by the inhibition of tissue phosphodiesterase, but probably reflects oxybutynin's local anesthetic properties and associated effects on Ca++ fluxes and binding.

Animals↗

PubMed1979

Investigation of the mechanism of decreased sensitivity of the rat seminal vesicle to norepinephrine by lithium.

Li+ is reported to reduce sensitivity of alpha-adrenergic receptors to NE. The present investigation was designed to investigate the mechanism of this decreased sensitivity on the rat isolated seminal vesicle. In innervated preparations, 1.35 X 10(-3) M Li+ (i) shifted the concentration-response curves of NE, methoxamine, ACh and BaCl2 to the right and reduced their maximum responses; (ii) antagonized the leftward shift and the enhancement of maximum responses to NE by cocaine (2.9 X 10(-4) M), and (iii) reduced only the maximum responses to KCl. In denervated preparations, 1.35 X 10 (-3) M Li+ shifted the concentration response curve of NE to the left without any change in the maximum responses. The antagonistic effects of Li+ on maximal responses to NE, ACh and KCl observed in innervated preparations were significantly increased in Ca++-free medium. Li+ (1.35 X 10(-3) M) increased NE uptake by the seminal vesicle significantly. It is concluded that decreased sensitivity of the seminal vesicle to NE by Li+ could be due to an increase in the uptake of NE and to a nonspecific postsynaptic spasmolytic action.

Acetylcholine↗

PubMed1981

Reproterol and the muscle of the trachea and bronchi: in vitro and in vivo comparative studies with various drugs used in the treatment of asthma.

In vitro in vivo reproterol showed intense spasmolytic effects upon the trachea and bronchi against various spasm-including agents (histamine, acetylcholine, acetyl-beta-methylcholine, 5-hydroxytryptamine, BaCl2). A comparative study with various drug used in the treatment of asthma (isoprenaline, metaproterenol, salbutamol, clenbuterol, papaverine and atropine) has been conducted.

Animals↗

PubMed1989

Effect of glucagon on sphincter of Oddi motor activity.

In this study the effects of glucagon 1-29 peptide and the metabolically inactive portion glucagon 1-21 have been evaluated on sphincter of Oddi (SO) motor activity. A triple lumen catheter perfused by a minimally compliant infusion system was used to record intraoddian pressures at endoscopy. A strictly blind evaluation of tracings was performed. Neither peptide administration appeared to induce any relevant variation of SO resting pressure nor frequency, amplitude and duration of phasic contractions. Data of the present study would not support the use of glucagon whenever a spasmolytic effect on the SO is looked for.

Adult↗

PubMed1989

Comparative study of the effects of cimetropium bromide and atropine on human esophageal motor functions.

The effects of atropine and cimetropium bromide, a new antimuscarinic compound with strong spasmolytic properties, were studied on human esophageal motility. Twenty healthy subjects underwent esophageal manometry with continuous monitoring of lower esophageal sphincter pressure (LESP), and of amplitude, duration and velocity of contractions of the esophageal body. After a 30-min basal period, atropine (12 micrograms/kg) or cimetropium (5 mg) were administered as an intravenous bolus in a cross-over random manner and the recording was continued for another 60 min. Twenty minutes after injection, atropine and cimetropium decreased maximally, in a similar extent, both the amplitude of contractions of the esophageal body (-65% of the basal values) and the LESP (-30% of the basal values). The duration and propagation velocity of the esophageal contractions did not change significantly after both drugs. Sixty minutes after injection of cimetropium, the amplitude of contractions of the esophageal body and LESP returned to basal values while atropine still reduced both variables. These findings indicate that cimetropium bromide has an inhibitory effect on LESP and on the amplitude of contractions of the esophageal body similar to atropine, but its action lasts less time.

Adult↗

PubMed1982

Bordetella pertussis-induced impairment of relaxation of rat trachea to isoprenaline and histamine and its reversal with hydrocortisone.

Bordetella pertussis vaccination of rats resulted in impairment of relaxation to isoprenaline and histamine of partially contracted tracheal smooth muscle. The concentration range of carbachol (10(-6) to 5 x 10(-6) M) required for contraction (ED50) did not differ from the control group. Pretreatment of vaccinated animals with hydrocortisone was found to reverse the inhibition of spasmolytic activity.

Animals↗

PubMed1992

Inhibitory effect of NZ-107 on anaphylactic bronchoconstriction in guinea pigs and rats.

We studied the effect of NZ-107 in a number of animal models of anaphylactic bronchoconstriction. In conscious guinea pigs, pretreated with indomethacin, pyrilamine and propranolol, passively sensitized with heterologous anti serum, NZ-107 in doses of 10-30 mg/kg per os inhibited the aerosolized antigen-induced cough and collapse. NZ-107 in a high dose of 100 mg/kg per os significantly prevented aerosolized antigen-induced anaphylactic collapse, but not cough in actively or passively sensitized conscious guinea pigs and also significantly protected aerosolized histamine-induced collapse, but not cough in conscious guinea pigs. This compound had little inhibitory effect on aerosolized acetylcholine-induced cough and collapse. In anesthetized animals, the effect of NZ-107 on bronchoconstriction induced by intravenous administration of antigen and various agonists was examined by the method of Konzett and Rössler. In doses of 10-50 mg/kg per os, NZ-107 inhibited antigen-induced bronchoconstriction in anesthetized guinea pigs. NZ-107 when intravenously administered to the anesthetized guinea pigs inhibited not only leukotriene D4-induced bronchoconstriction, but also thromboxane A2 mimetic U-46619-, platelet-activating factor- and histamine-induced bronchoconstriction. In anesthetized rats, NZ-107 in a dose of 300 mg/kg per os tended to inhibit the antigen-induced bronchoconstriction, but this effect was not significant. These results indicate that NZ-107 acts as a spasmolytic agent which inhibits bronchial responses to antigens or various other bronchoconstrictors in animal models, suggesting that NZ-107 may be potentially beneficial in the treatment of bronchial asthma.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1978

[Myotropic spasmolysis in the treatment of ureteric colics (author's transl)].

The effectiveness of parasympathicolytic drugs in the treatment of ureteric colics is doubtful. Bencyclane is a new myotropic substance. Its spasmolytic effect on smooth muscle is five times stronger than that of papaverine. The results of the clinical use of Bencyclane in cases of ureteric colic are described and discussed.

Bencyclane↗

PubMed1981

Cystometry and UPP measurement under fluoroscopic visualization by means of X-ray television in patients with a traumatic spinal cord lesion.

At the beginning of urination training in 38 patients with traumatic spinal cord lesion, who were in an early recovery stadium, the UPP measurement under an evacuated bladder state, cystometry and the UPP measurement repeated again with a full bladder were investigated. These investigations indicated the possibility of how to achieve the urination training, the indication for proper medication, antiadrenergic or other spasmolytic drugs and the determination of the proper site, bladder neck or external urethral sphincter, for transurethral operation, if necessary. Moreover, the results of these measurements were divided into 3 groups, according to the change of the UPP curve and the state of the cervical portion of the bladder (shut or open), with bladder filling (cystometry).

Adolescent↗