Muscle relaxants synthetic

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

The estimated sensitivity of skin tests for muscle relaxants is approximately 94-97%. Sensitivity for other substances varies. It is good for synthetic gelatins, (3-lactams, but poor for barbiturates, opioids and benzodiazepines dyes, and chlorhexidine. 

The opiate alkaloid, papaverine, from Papaver somniferum is an anti-spasmodic, vasodilator, and smooth muscle relaxant. Its total synthesis has been studied since Pictet and Gams early work in 1909 and has since been followed up by various industrial syntheses up till the early 1950s using important industrial commodities as vanillin, acetovanillone, veratraldehyde (methylvanillin), and homoveratric acid as starting materials (see Figure 4.50). Table 4.23 summarizes the results of the five synthetic plans for this natural product. All are convergent... 

Much debate has been waged over medicinal uses of cannabis. Several therapeutic uses have been proposed, including antiemetic, analgesic, appetite stimulant, and muscle relaxant. A synthetic cannabinoid, dronabinol (Marinol) has been marketed for clinical treatment of appetite loss, nausea, and vomiting. Although synthetic, it is identical to the main psychoactive chemical constituent of cannabis (A9-THC). 

The production of a quaternary ammonium salt from a tertiary amine and an alkyl halide forms the synthetic route to decamethonium, the first of a range of synthetic muscle relaxants having an action like the natural materials found in the arrow-poison curare. Decamethonium is actually a di-quaternary salt, as are more modem analogues, such as suxamethonium. Suxamethonium superseded decamethonium as a drug because it has a shorter and more desirable duration of action in the body. This arise because it can be metabolized by ester-hydrolysing enzymes (esterases) (see also Box 6.9). 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic effect. 

Atracurium is a synthetic bisquaternary benzylisoquinolinium compound with a novel method of metabolism, the Hofmann elimination reaction. This reaction takes place at a pH of 7.4 and a temperature of 37°C. It is thus metabolised at body temperature and pH, and has to be stored in a refrigerator. The usual intubating dose of atracurium is 0.5-0.75 mg-kg-1 (2-3xED95). The onset of action with this dose is 2-3 minutes and intubating conditions are acceptable in 90-120 seconds. Spontaneous recovery occurs reliably from an atracurium neuromuscular block, such that an intubating dose of about 0.5 mg-kg-1 can be expected to provide surgical muscle relaxation for 25-40 minutes in the normal healthy patient. Repeated administration of atracurium leads only to a small increase in the duration of action. 

Gallamine is a synthetic muscle relaxant as are several analogs of curare. 

It is known that pyrazolines and pyrazoles are an important class of pharmacophores [1,2,3,4, 5,6], Heterocycles containing these fragments are important targets in synthetic and medicinal chemistry since they are key moieties in numerous biologically active compounds possessing tranquilizing, muscle relaxant, psychoanaleptic, anticonvulsant and antidepressant activities [7, 8, 9,10,11,12], This includes kinesin spindle protein [12] and monoamine oxidase [13, 14] inhibitors as well as antimycobacterial [15, 16] and anti-inflammatory [17] agents. 

Decamethonium (Figure 6.49) was the first synthetic curare-like muscle relaxant, but has since been superseded. In tubocurarine, the two nitrogens are also separated by ten atoms, and at physiological pHs it is likely that both centres will be positively charged. Obviously, the interatomic distance (1.4 nm in tubocurarine) is very dependent on the structure and stereochemistry rather than just the number of atoms separating the centres, but an extended conformation of decamethonium approximates to this distance. Suxamethonium... 

The toxiferines (see Figure 6.85, page 359) also share the diquaternary character. Alcuronium is a semi-synthetic skeletal muscle relaxant containing the dimeric strychnine-like structure and is produced chemically from C-toxiferine (see page 360). 

Papaverine is a commonly known opium alkaloid that is a smooth muscle relaxant and is used as a coronary vasodilator [2]. Scheme 5 shows the synthetic route to papaverine proposed by Pictet and Gams [21] almost a century ago [2]. 

Amino-2,l-benzisothiazoles possess analgesic, antipyretic, tran-quilizing, and muscle-relaxant properties.100-103 The 3-methylamino derivative, in particular, displays potent gastric antisecretory activity.101,129 Diazotization of 3-amino-2,l-benzisothiazoles and coupling with tertiary aromatic amines yield a variety of azo dyes especially suitable for disperse dyeing of synthetic polymer fibers 116,117, n -121.13°. i 1... 

Benzoquinonium] (quaternary ammonium benzoquinone) Synthetic nACh-R agonist at non-ACh site (at 1) [skeletal muscle relaxant]... 

The first muscle relaxant to be discovered and clinically used was d-tubocurarine (Figure 9.14a), which is found in curare, an arrow poison that was used by South American natives. Quite a bit of imagination is required to spot any stmctural resemblance to acetylcholine d-tubocurarine is much larger and contains not one but two quaternary amines within a rather large, rigid ring stmcture. The resemblance is more readily spotted with the more recent, synthetic compound pancuronium (Figure 9.14a). This molecule has two acetylcholine moieties, embedded in a... 

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