Muscle relaxants. See

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

The quaternary ammonium compounds paraquat and diquat are widely used non-selective contact herbicides, which are extremely toxic to humans. Fee et al. [112] established an HPLC-MS-MS procedure for the determination of these herbicides in whole blood and urine using ethyl paraquat as internal standard. After extraction with Sep-Pak C18 cartridges, analytes were separated using ion pair chromatography with heptafluorobutyric acid in 20 mM ammonium acetate and acetonitrile gradient elution. Detection was carried out in ESI MS-MS SRM mode. Using similar separation and detection conditions, paraquat, diquat, difenzoquat, and a number of structurally related quaternary nitrogen muscle relaxants (see Section 20.2.1.3) were determined in whole blood by Ariffin and Anderson [113]. 

Note. For a review of the pharmacokinetics of alcuronium chloride and other muscle relaxants, see M. I. Ramzan et al, Clin. Pharmacokinet., 1981, 6, 25-60. 

Figure 19-3 Mechanism of nitrovasodilators Nitric oxide (NO) formed in smooth muscle from nitrovasodilators or from endothelial cells (EDRF) activates guanylate cyclase (GC ). GC activates cGMP-dependent protein kinases that phosphorylate myosin light-chain kinase (MLCK), causing its inactivation and subsequent muscle relaxation (see also Fig. 19-2)...

GABAj receptors are of the seven-transmembrane G-protein-coupled type, and they have a widespread distribution in the body. Agonists at this receptor site include L-baclofen, CGP 27492 and CGP 35024. The receptors are negatively coupled to cAMP, and typical responses in neurons are to inhibit excitability by opening potassium channels or closing calcium channels. These inhibitory actions can be harnessed clinically for instance, baclofen is used as a muscle relaxant and has actions mainly at the spinal level within the GNS (see SKELETAL MUSCLE RELAXANTS). See GABA RECEPTOR ANTAGONISTS. 

Edrophonium chloride, a cholinesterase inhibitor (10 mg IV given over 30 to 45 seconds), may be used as a curare antagonist (to reverse neuromuscular blocking action), and for reversal of nondepolarizing muscle relaxants (see also Figures 17 and 79). 

Administration of quinidine shortly after recovery may produce recurrent paranalysis. The use of magnesium sulfate in preeclamptic patients potentiates the effects of both depolarizing and nondepolarizing muscle relaxants (see also Figme 99). 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

For enhanced CNS effects with alcohol with other muscle relaxants, see benzodiazepines , (p.53), meprobamate , (p.68), and tizanidine , (p.l287). 

---