Spasmolytic activity

According to Nyman the pharmacological action of hyoscine is considerably modified in the quaternary compounds of the alkaloid, e.g., the inhibiting action on salivary secretion is greatly increased in the methonitrate, as is also the spasmolytic activity, but the mydriatic action is unchanged and the central sedative activity disappears. 

Acylation of benzamidoxlme (144) with chloropropionyl chloride gives the 0-acylated derivative (145). Reaction of that intermediate with diethylamine serves first to cyclize the molecule to the 1,2,4-oxadiazole heterocycle subsequent displacement of the halogen on the side chain gives oxolamine (146),a drug with antltussive and spasmolytic activity. 

One of the few nonnitrogenous compounds to show spasmolytic activity is a rather simple chromone. Acylation of the phenolic ketone, 31, with the half ester-half acid chloride from oxalic... 

ROJAS A, BAH M, ROJAS J I, SERRANO V, PACHECO s (1999) Spasmolytic activity of some plants used by the Otomi Indians of Queretaro (Mexico) for the treatment of gastrointestinal... 

Melzig MF, Pertz HH, Krenn L. Anti-inflammatory and spasmolytic activity of extracts from Droserae herba. Phytomedicine 2001 8 225-229. 

In mast cells, histamine release induced by IgE or A23187 was also inhibited by feverfew extract [48] which also reduced spasmolytic activity of smooth muscle induced by acetylcholine, 5HT, histamine, prostaglandin E2 and bradykinin [20]. 

With sulfur and triethylamine in dimethylformamide, compounds (86) give (89) (Equation (21)) <89JPR243>. With thiols or KjS, sulfides are produced (e.g., (90) and (91)), which show spasmolytic activity in vitro <86MI 404-01 >. Smooth 5N2-displacements of chlorine occur with phenol, thiophenol, SCN, and thiourea in dimethylsulfoxide. However, with K2CO3 or sodium cyanide, (86) (Ar = Ph) affords the trimers (92) or (93) (Scheme 32). With electron-deficient trans alkenes, stereoselective formation of cyclopropanes (94) was observed (Scheme 32). No reactions occur with maleates <66HCA412>. 

Spasmolytic activity. Ethanol (95%), ethanol/glycerin, and glycerin extracts of the leaf, administered to guinea pigs at a dose of 50 mg/kg, was active vs vasopressin-induced coronary spasms as determined from electrocardiogram ". Ethanol (30%) extract of the dried leaf, administered to rabbits at a concentration of 1 mg/mL, was active on aorta vs K -induced contractions ". Decoction of the dried leaf, administered to rats, was active on aorta, IC501.12 mg/mL. The effect of the lyophilized extract on phenylephrine-induced contraction and endothelium was present. Decoction of the dried leaf, administered to rats, was active on the aorta vs phenylephrine-induced contraction, IC501.16 mg/mL. Water extract of the dried leaf, administered to rats at a dose of 3 mg/mL, was active on trachea vs acetylcholine-induced contractions ". Superoxide production inhibition. Seed oil, administered to rats at a concentration... 

Cantabrana. Spasmolytic activity of a lipidic extract from Sabal serrulata SR074 fruits further study of the mechanisms underlying this activity. Planta Med 1996 62(6) 507-511. 

The antimycotic activity of a number of substituted 3-(3,3,3-trichloro-2-hydroxyprop-l-yl)benzofurans has been reported. Diuretic and other activities have been observed in a number of substituted aminobenzofuran-2-carboxylic acid derivatives. a- 2-Benzofuranyl) acrylic acid has exhibited a marked depressive ataratic and hypotensive activity (61MI31200), while 5-cinnamoylbenzofurans, e.g. (499), have been examined for hypertensive, vasodilating and spasmolytic activities (70GEP1933178). 

Table 11. Acute toxicities and spasmolytic activities of 96a/96b-99a/99b7S)...

Table 13. Spasmolytic activities of 150b— 153b and 151a on the isolated guinea pig ileum...

Substitution of oxygen in the Si—0—C system by the isoelectronic CH2 group leads to stable compounds with a decreased but prolonged antihistaminic, anticholinergic and antitremorine activity. Replacement of the oxygen atom by a NH group leads to compounds, showing no spasmolytic activity at all because of rapid hydrolysis of the Si—N bond. 

Silicon Containing Derivatives of Aminosubstituted Tertiary Alcohols with Spasmolytic Activity... 

Artemisia abrotanum Four flavonols isolated from A. abrotanum reportedly possess spasmolytic activity. These flavonols show a dose-dependent relaxing effect on the carbacholine-induced contraction of trachea. Its therapeutic efficacy is not known. 

Collagen synthesis increased in the pulmonary arteries of rats which had been treated with monocrotaline.70 Doronine has an hypotensive effect when administered to cats.71 Senecionine and otosenine showed spasmolytic activity on the intestinal smooth muscles of mice.72... 

Baclofen exerts its spasmolytic activity at GABAb receptors. Activation of these receptors in the brain by baclofen results in hyperpolarization, probably by increased K+ conductance. It has been suggested that hyperpolarization (in the spinal cord as well as in the brain) causes presynaptic inhibition by reducing calcium influx (Figure 27-11) and reduces the release of excitatory transmitters in both the brain and the spinal cord. Baclofen may also reduce pain in patients with spasticity, perhaps by inhibiting the release of substance P in the spinal cord. 

Dantrolene is a hydantoin derivative related to phenytoin that has a unique mechanism of spasmolytic activity. In contrast to the centrally active drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers. The normal contractile response involves release of calcium from its stores in the sarcoplasmic reticulum (see Figures 13-1 and 27-10). This activator calcium brings about the tension-generating interaction of actin with myosin. Calcium is released from the sarcoplasmic reticulum via a calcium channel, sometimes called the ryanodine receptor channel because the plant alkaloid ryanodine combines with a receptor on the channel protein and, in the case of the skeletal muscle channel, locks it in the open position. 

Takatonine (5,6,7,4 -tetramethoxy-l-benzylisoquinoline) had a weak atropine-like and papaverine-like effect (370). Its spasmolytic activity was determined on isolated smooth muscle preparations of guinea pig ileum and mouse small intestine. 

Let s quickly juxtapose this result with an enantiomer case having a different outcome. In re Adamson resulted from an appeal to the CCPA of denial of patentability by the USPTO Board of Appeals, which rejected claims 1-11 of the applicant s application directed to compounds having spasmolytic activity and processes for making same.75 The stated reason for the rejection is that the compounds were obvious in view of the prior art disclosure of the racemic mixture. Claim 1, which was deemed by the court to be a typical claim of the invention, is reproduced in Figure 8.19 together with the structures of the claimed compounds. 

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