Relaxant Activity

Benzodiazepines enhance presynaptic inhibition by releasing GABA from intemeurons and by facilitating the action of glycine in the spinal cord and brain stem. Glutamate and aspartate have 

When both GAGA and BZ sites are occupied, neuronal excitability is reduced 

FIGURE 65.6 Diazepam opens the chloride channel. BZ = benzodiazepine GABA = y-aminobutyric acid. 

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Substitution of additional basic groups onto a closely related nucleus affords a compound with muscle relaxant activity with some activity in the treatment of angina. Reaction of the... 

When the side chain involves an unsymmetrical urea moiety, muscle relaxant activity is often seen. One such agent, 1 id-amidi ne ( ) exerts its activity as an anti peristaltic agent. Its synthesis involves the straightforward reaction of 2,6-di-... 

Muscle relaxant activity is found in the aminoxy-methylnaphthalene structure of nafomine (27). The synthesis proceeds from l-chloromethyl-2-methylnaph-thalene (26), which is reacted with N-carbethoxy-hydroxylamine and base. In this way, the basic nitrogen is protected as the carbamate. Loss of the carbethoxy group either during reaction or on workup affords nafomine (27).10... 

Quinazolines containing an electron-rich carbocyclic ring have been associated with smooth muscle relaxant activity. The mechanism of action (phosphodiesterase inhibition, a- adrenergic blockade) and organ selectivity (bronchi, vascular smooth muscle) vary greatly with substitution on the heterocyclic ring. 

Reduction of the exocylic double bond and inclusion of the side chain nitrogen in a piperidine ring leads to a compound (19) which exhibits skeletal muscle relaxant activity. Its one step synthesis begins with reaction of thioxanthene (17) with phenyl sodium... 

Yemitan OK, Salahdeen HM. Neurosedative and muscle relaxant activities of aqueous extract of Bryophyllum pinnatum. Fitoterapia 2005 76 187-193. 

Avoid trying to force sleep if you do not fall asleep within 20-30 minutes, leave the bed and perform a relaxing activity (e.g, read, listen to music, or watch television) until drowsy. Repeat this as often as... 

For several pyridazine derivatives reported in the patent literature a muscle relaxant activity has been claimed. In this context, oxadiazolylpyridazines (35) [117] and 6-aryl-4,5-dihydropyridazine-3(2/f)-ones bearing various functionalized alkyl side-chains at N-2 [163, 174, 188, 189] are to be mentioned. Denpidazone (56) (CAS 42438-73-3), a l,2-diphenylpyridazine-3,6-dione derivative, is listed as a muscle relaxant [96]. 

While the individual drugs in the benzodiazepine group differ in potency, all benzodiazepines in common use have anxiolytic, sedative-hypnotic, anticonvulsant and muscle-relaxant activity in ascending order of dose. The main clinical difference between the individual drugs lies in the time of onset of their therapeutic effect, and the intensity and duration of their clinical activity. 

Modification of the substitution pattern on the same chromone gives a compound with smooth muscle relaxant activity, flavoxate (184). The synthesis of this flavone ester is initiated with methylation of the hydroxypropiophenone 177 to 178 followed by reduction of the nitro group to yield aniline 179. 

Agents affecting the central nervous system and have muscle relaxant activity together with a unique mechanism of action, i.e. dantrolene, will be briefly discussed here. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

Smooth muscle relaxant activity. Ethanol (95%) and water extracts of the dried aerial parts, at a concentration of 1 1, produced weak activity on the rabbit duodenum. The ethanol extract was equivocal on the guinea pig ileum k Petroleum ether extract of the dried entire plant, administered intraperi-... 

Skeletal muscle relaxant activity. Petroleum ether fraction chromatographed and fraction eluted with chloroform, at a concentration of 0.50 mg/mL, was inactive on the frog rectus abdominus muscle vs ACh-induced contractions . 

Smooth muscle relaxant activity. Alkaloid fraction (tertiary) of the dried seed, at a concentration of 25 pg/mL was active on the rabbit and rat ileum . 

Smooth muscle relaxant activity. Tine-ture of the gland, administered to rabbits, was active on the bladder and intestine " . Toxic effect. Gum, administered orally to adults, was active. A case of methemoglobinemia occurred in a 5-week-old male infant, after administration of asafetida preparation to alleviate colic. Treatment was with intravenous methylene blue and the infant recovered . Tumor-promoting activity. Water extract of the dried oleoresin, administered externally to mice at a dose of 200 pL/animal, was active vs 7,12-dimethylbenz[a]anthra-cene and croton oil treatment ". ... 

Smooth muscle relaxant activity. Hexane extract of the dried fruit, administered to guinea pigs at a concentration of 0.15 mg/ mL, was active on bladder and ileum vs KCl-induced contractions R . Administration to... 

Smooth muscle relaxant activity. The essential oil was active on the guinea pig trachea and ileum, ED , 171 and 36 mg/L, respectively . 

The subunits can exist in two forms, termed the T-form and the R-form. The R-form ( relaxed ) is the relaxed, active state the T-form ( tense ) is the less active state. T and R forms are in equUibrium with each other, independent of whether the ligand is boimd or not. 

Botox (Toxin) Muscle relaxation activity, cervical dystonia Botulinum sp. 

C) The lower relaxant activity exhibited by flavanones against the contractions induced by any of the agonists tested, as compared with the others flavonoids, suggests that the presence of a double linkage C2-C3... 

Silicon Containing Carbamates with Muscle Relaxant Activity... 

All compounds, with the exception of 64a, 64b and 65a, exhibited sublethal activities in the rotating rod test. The phenyl-substituted derivatives 76, 77 and 78 also showed muscle relaxant activity of a short duration70) when tested by the same animal model (cf. Table 10). 

Dihydro-6//-[l]benzopyrano[3,4-c][l, 5]benzothiazepines (153) were prepared by cyclocondensation of 5 with 2,3-dihydro-3-dimethylami-nomethyl-4//-1 -benzopyran-4-one (152). Compounds 153 were reduced and alkylated to derivatives 154, which demonstrated sedative and muscle-relaxant activities (Scheme 48) (73FRP2150807). 

Quaternary ammonium salts of dantrolene and clodanolene have been prepared, and the effect of the organic cation on the aqueous solubility has been reported (Ellis et al., 1980). It was reasoned that since the hydantoin moiety in each drug is weakly acidic, a strong base should be found for salt formation. The 13 different quaternary ammonium compounds were therefore used in the hydroxide salt form. The acid-base reaction proceeded rapidly, and the salt products were stable during recrystallization steps. Of the four salts for clodanolene, the aqueous solubilities ranged from 2- to 100-fold that of clodanolene sodium, on a mass basis. Of the 11 salts for dantrolene, the benzyl-trimethyl ammonium salt exhibited comparable solubility to that of dantrolene sodium. Among the other 10 salts were several examples that yielded enhanced solubilities of up to 1000-fold that of the sodium salt. Twelve of the Lfteen salts successfully demonstrated muscle relaxant activity when administered orally. 

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