Papaverine antispasmodic

Mechanism of Action Ananticholinergicthat exerts antispasmodic (papaverine-like) and antimuscarinic (atropine-like) action on the detrusor smooth muscle of the bladder. Therapeutic Effect Increases bladder capacity and delays desire to void. Pharmacokinetics ... 

Opium alkaloids are nonpeptide agonists for the opioid peptide hormone receptors. The dried latex of Papaver somniferum (opium), or the seed capsule of the plant itself, are the sources of almost 25 alkaloids. Some simple isoquinolines from opium, like papaverine (5.86), are antispasmodics. The principal alkaloid ( 10% of the total) is morphine (3.11), which is also an isoquinoline (rings C and E) but can addihonally be considered a phenanthrene derivahve (rings A, B, and C). 

Papaver somniferum L. Yu Mei Ku (Opium poppy) (whole plant) Berberine, codeine, papaverine, isocorypalmine, laudanine, magnoflorine, meconine, 6-methylocodine, morphine, narcotine, pseudomorphine, rhoeadine, sanguinarine, beta-sitosterol, stigmasterol, thebaine, zanthaline.50 Antitussive, antispasmodic, analgesic, astringent, narcotic, treat chronic enteritis, diarrhea, enterorrhagia, headache, toothache, asthma. 

The amounts of these alkaloids in opium vary greatly with growing conditions and regions. Of the above, only noscapine and papaverine have no narcotic properties. Papaverine has found some medicinal use as an antispasmodic and cerebral vasodilator, and noscapine found use a few decades ago in antitussive preparations. 

Papaverine is one of the few commercial alkaloids synthesized, rather than isolated. It is used either alone for various vascular disorders or in combination as an antispasmodic. The several classes of... 

The gasiroinie.slinal (Gl) aniispasmodic properties of bisaboloi and its oxides are well known. In fact, bisaboloi is said to be as potent as papaverine in tests of muscle spasticity. Besides bisaboloi. the flavone and coumarin components have -antispasmodic activities. The blue compound chamazulene posse.sses both anti-inflammatory and antiallcigenic ac-tivitic.s. as do the water-soluble components (the flavonoids). Apigenin and lutcolin possess anti-inflammatory potencies similar to that of indtimethacin. These flavonoids possess acidic phenolic groups, a. spacer, and an aromatic moiety that could fit into the COX receptor. None of the.se effects has been unequivocally documented in humans. The essential oil posse.s.ses low water. solubility, but teas used over a long period of time provide a cumulative medicinal effect. Typically. I teaspoon (3 g) of flower head is boiled in hot water for IS minutes. 4 times a day. 

Chamomile tea produced from the flowers of Matricaria, recutita has long been used as an antispasmodic for gastric and menstrual cramps. Studies with guinea-pig ileum have shown that the water-soluble flavonoid fraction and especially apigenin has antispasmodic activity three times that of papaverine. 

Clinically, papaverine is used as an antispasmodic, and is given by mouth or by vein in doses of 30 to 80 mg. It has been found useful in the treatment of spastic conditions of the stomach and intestines caused by hyperacidity and duodenal ulcers. Other applications, such as in the treatment of biliary colic, asthma, vascular spasms, including angina pectoris, spasm secondary to embolic phenomena, and peripheral vascular diseases, have been more or less abandoned, and several synthetic antispasmodics have made inroads on the fields formerly reserved for papaverine. However, a shortage of papaverine developed when its usefulness was at a peak, and several methods were developed for the industrial synthetic production of the alkaloid to take care of this condition (see p. 43). A brief selected bibliography may serve as a guide to the literature concerning the clinical application of papaverine (68). 

Table 2 shows most of the papaverine analogues tested as antispasmodics, together with any reported results of the tests. 

Additional pharmacological data taken from the comprehensive report of Dobrowsky (22b) are shown in Tables 3 and 4. One compound mentioned in this work, l-(3-pyridyl)-3-methyl-6,7-methylenedioxyisoquin-oline (XLII) should be mentioned separately it is about as toxic although more irritating than papaverine, but exhibits about 20 times the antispasmodic activity of the alkaloid on the isolated strip of rabbit intestine. This is in contrast to the much lower activity (2 to 5 times papaverine) observed for the isomeric 3-picolyl derivative (XLIII) (72b). 

TOXICITY, ANTISPASMODIC ACTIVITY, AND LOCAL ANESTHETIC ACTIVITY OF SOME PAPAVERINE DERIVATIVES... 

Papaverine. The BIA papaverine is a minor (about 1%) component in most the opium varieties of P. somniferum and used as a vasodilator, a muscle relaxant, and an antispasmodic. Controversial information exists on the papaverine biosynthesis pathway. Two putative pathways have been proposed (Figure 6.22). The first one involves fV-desmethyl intermediates and utilizes (5)-coclaurine, which is transformed, under the control of 3 -hydroxylase (3 -OHase), into (5)-methylnorlaudanosoline. The latter undergoes three consecutive methylation steps leading to (5)-tetrahydropapaverine through the successive mediations of 3 -OMT 4 -OMT, and norreticuline 7-0-methyltransferase (N70MT). (5)-Tetrahydropapaverine is finally converted fo papaverine by dehydrogenase (deHase) enzymes. 

Luisa Martin, M., Teresa Diaz, M., Jose Montero, M., Prieto, P., Luis San Roman and Diego Cortes 1993, Antispasmodic activity of benzyliso-quinoline alkaloids analogous to papaverine , Planta Medica 59 63-67. 

The four benzylisoquinolines of clinical interest are papaverine, used as an antispasmodic and peripheral vasodilator dioxyline, also a peripheral and coronary vasodilator the closely related ethaverine, which is another smooth muscle relaxant and trimetoquinol, which is a bronchodilator. Several new analogs of these compounds have been screened for pharmacological activity. ... 

Colourless needles with blue fluor. from MeOH. M.p. 141°. Employed as substitute for papaverine. Salts used as antispasmodics and sraatives. 

The fruit of Lycium chinense was found to afford significant protection against carbon tetrachloride-induced toxicity in cultures of rat hepatocytes. Zeaxanthin and physalein could be identified as active components their activities turned out to be comparable to that of the clinically estabhshed drug silybin (Kim et al. 1997). An antispasmodic activity of the apocarotenoid P-damascenone was observed as a result of bioassay-guided fractionation of the leaves of I. pes-caprae. It turned out be as potent as the established drug papaverine (Pongprayoon et al. 1992). 

Ergometrine powerfully stimulates the smooth muscle of the uterus, and constricts the muscular fibres of blood-vessels. Papaverine, a poppy alkaloid, has a direct antispasmodic action on gut muscle. A number of simple aliphatic amidines, guanidines, woureas, and / othioureas, all of which are strong bases, raise blood-pressure and contract the intestine by direct action (Pastier, 1949). These substances are not blocked by antihistaminics. 

---