Spasmolytic drugs

It has been stated already (atropine, p. 112) that there are two types of spasmolytic drug, the neurotropic, typified by atropine, and the musculo-tropic or myotropic to which papaverine belongs. In laboratory work the two types are usually tested against spasm induced by acetylcholine and... 

Reviews of recent work on spasmolytic drugs have been published by Raymond and by Blicke, and a detailed account of the action of papaverine and its derivatives, including laudanosine and laudanine with numerous references to literature is given by Krueger, Eddy and bumwalt. ... 

In contrast to GABA itself, benzodiazepines and other sedative-hypnotics have a low affinity for GABAB receptors, which are activated by the spasmolytic drug baclofen (see Chapters 21 and 27). 

A rare interaction of succinylcholine with volatile anesthetics results in malignant hyperthermia, a condition caused by abnormal release of calcium from stores in skeletal muscle. This condition is treated with dantrolene and is discussed below under Spasmolytic Drugs and in Chapter 16. 

In re Adamson, 275 F.2d 952 (CCPA 1960). A spasmolytic drug is used to prevent muscle spasms, particularly spasms in smooth muscle. 

Shallek, V. and Smith, T H. F. 1952 Electroence(dialographlc analysis of side effects of spasmolytic drugs J. Fhazmacol. Exp. therap. 104 291-298. 

Schallek, V, Smith, T.H.F. 1952 Electroencephalographlc Analysis of Side Effects of Spasmolytic Drugs J. Pharmacol. Exp Therap. 104 292-298 ... 

ANTISPASMODICS (spasmolytic drugs) relieve spasm in smooth muscle, e.g. in the intestine, bladder and airways. 

Tortoriello and Aguilar-Santamaria [120] investigated in detail the spasmolytic mechanisms of action of one of these plants, B. serraefolia. The results suggest that the extract does not interact with classical receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intracellular store. Different chemical compounds, such as clerodane diterpenes and flavonoids, which are typical constituents from the Baccharis genus, have been considered as the active principles of many spasmolytic drugs. A bioassay-monitored fractionation of an extract from B. genistelloides yielded a mixture that blocked the calcium-induced contractions of KCl-depolarized rat portal vein preparations [121], Pharmacological tests of two pure compounds isolated from the mixture revealed a dilactonic clerodane-diterpene, Fig. (70) as the active compound. 

GABAg receptors and 5-HTj receptors share the same potassium ion channel, with a G protein involved in the coupling mechanism. The spasmolytic drug baclofen is an activator of GABAg receptors in the spinal cord. The anxiolytic drug buspirone may act as a partial agonist at brain 5-HTj receptors. The answer is (C). 

Mechanism of action The spasmolytic drugs act by several mechanisms. Three of the drugs act in the spinal cord. Diazepam facilitates GABA-mediated presynaptic inhibition, and baclofen acts as a GABAg agonist. Tizanidine, an imidazoline related to clonidine, reinforces both presynaptic and postsynaptic inhibition in the cord. All three drugs reduce the tonic output of the primary spinal motoneurons. 

Spasmolytic drugs Diazepam, baclofen, dantrolene, tizanidine, botulinum toxin Cyclobenzaprine ... 

Regarding the spasmolytic drugs, which one of the following statements is false ... 

Hypotension may occur with tubocurarine and with the spasmolytic drug tizanidine. In the case of tubocurarine, the decrease in blood pressure may be due partly to histamine release and also to ganglionic blockade. Tizanidine causes hypotension via alpha2 adrenoceptor activation like its congener clonidine. The answer is (D). 

Chromatographic separation of papaverine has been studied in recent years (7), and the increasing importance of the compound as a spasmolytic drug has led to renewed efforts to simplify its purification procedure (8). 

Papaverine (12) is an excellent spasmolytic drug which relaxes the smooth muscle of blood vessels. It especially inhibits contractions brought about by direct stimulation of smooth muscle of the g.i. tract. Activity against spasms produced by the transmitter of parasympathetic impulses, acetylcholine, is only possible when much higher doses are used. An advantage of papaverine is that spasms are removed with small doses but without influencing the normal tone and peristaltic activity of the g.i. tract. Papaverine is combined with atropine in many medicinal preparations used against colic. Coronary arteries are dilated by papaverine as well as peripheral vessels, especially those of the g.i. tract. Thus, blood pressure can be suddenly... 

Enantiomerically enriched, tertiary alcohols could also be constructed by addition of Al(2-thienyl)3(THF), mediated by the same catalyst system [93]. Several aryl,methyl ketones and an enone could frequently be transformed in almost quantitative yields and with ee s exceeding 90%. Again, 2-methoxyacetophenone furnished only a moderate ee of 45%, and unfortunately, alkyl,methyl ketones (alkyl = nPr, Pr, nBu) were transformed all in 96% yield but with less than 17% ee. Conducting the reactions in toluene led to better results than in THF, and the optimized conditions allowed the stereoselective total synthesis of the anticholinergic/spasmolytic drug tiemonium iodide (50) in 84% yield over three steps from 48 (Scheme 9). 

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