Sedatives, Hypnotics, and Tranquillizers

Antidepressants Antipsychotic Agents Sedatives, Hypnotics, and Tranquilizers Anticonvulsants. 

III SEDATIVE, HYPNOTIC, AND ANXIOLYTIC DRUGS (TRANQUILIZERS AND SLEEPING PILLS)8... 

A. Additive depressant effects with other opioid agonists, ethanol and other sedative-hypnotic agents, tranquilizers, and antidepressants. 

Name and draw structural formulas for the products of the complete hydrolysis of meprobamate and phenobarbital in hot aqueous acid. Meprobamate is a tranquilizer prescribed under 58 different trade names. Phenobarbital is a long-acting sedative, hypnotic, and anticonvulsant. [Hint. Remember that, when heated, jS-dicarboxylic acids and /3-ketoacids undergo decarboxylation (Section 13.8B).]... 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

As already noted, there are drugs found among benzodiazepine derivatives that have expressed anxiolytic action and that lack or have poorly expressed sedative-hypnotic effects, which are called daytime tranquilizers. Medazepam, a representative of the daytime tranquilizers, is a drug that differs from diazepam only in the absence of a carbonyl group in the seven-membered azepine ring. 

A series of esters of nuclear halogenated 3-carboxy-1,2,3-benzotriazin-4(3//)-ones show depressant activity, while the benzoate esters of substituted 3-(2-hydroxyethyl)-l,2,3-benzotriazin-4(3f0-one are reported to function as coronary dUating agents," as do certain other compounds of this type." 3-(o-Haloaryl)-l,2,3-benzotriazin-4(3i/> ones are claimed to have antisecretory," anoretic, anticonvulsant, and hypoglycemic activity, and a variety of other 3-aryl derivatives are stated to be relaxants, tranquilizers, sedatives, hypnotics, or cramp inhibitors. A number of derivatives of 10, R = H, in which the 3-substituent is a long alkyl chain containing a terminal sulfonamide group have been claimed to act. as antidiabetics. ... 

Various dihydro-1,4-oxathiins and dihydro-1,4-dithiins are reported to be useful in areas other than agriculture. Thus, 2,3-dihydro-l,4-dithiin-5,6-dicarboximides display a wide spectrum of biological activity (77SST(4)332) while derivatives of the basic structure (243) have been patented as tranquilizers, anticonvulsants and hypnotics (76GEP2550163). Sedative, myorelaxant and cataleptic properties are associated with certain 2,1-benzoxathiane 2,2-dioxides (75BRP1383459). 

The term minor tranquilizer (which has been replaced by the more precise terms sedative-hypnotic or anxiolytic ) refers to drugs used to treat conditions such as insomnia and anxiety. Because they reduce anxiety and produce pleasantly sedating or tranquilizing effects, these drugs are more subject to abuse than the neuroleptics. 

The first sedative-hypnotic, or minor tranquilizer, bromide, originated in the 1860s. Bromides are long-acting sedatives that were rarely used past the turn of the nineteenth century however, bromide can still be found in Bromo Seltzer. The bromides are gastric irritants with a narrow safety margin and may cause a chronic toxicity known as bromism. 

Like the neuroleptics, all of the commonly used minor tranquilizers—with the possible exception of bus-pirone (BuSpar)—are CNS depressants. Unlike the neuroleptics, however, these drugs are called sedative-hypnotics because they produce relaxation (sedation) at lower doses and sleep (hypnosis) and eventually coma at higher ones. The anxiolytic (antianxiety) effect is merely an early stage of CNS depression. 

At high doses, both the major and minor tranquilizers are severely toxic and may cause coma, respiratory arrest, convulsions, acute renal failure, speech impairment, or death. However, at therapeutic doses, the neuroleptics have been associated with more severe, longterm side effects than the sedative-hypnotics. 

The sedatives or tranquilizers have a calming effect, while the hypnotics produce drowsiness and sleep. Sometimes referred to as solid alcohol, the sedative-hypnotics have an effect similar to that of alcohol. If you take a sleeping pill or sedative, in addition to making you drowsy, it affects your breathing, slows your reflexes, impairs muscular coordination, and lowers your inhibitions. Like alcohol, these drugs can impair your thinking, memory, and judgment. 

Flunitrazepam is a tranquilizer developed in the 1960s by Hoffmann-LaRoche, Inc., and first marketed under the trade name Rohypnol in Switzerland in 1975. It is a member of a class of drugs called the benzodiazepines, which includes drugs such as Librium , Xanax , and Valium. This family of sedative-hypnotic drugs is used to treat anxiety, convulsions, muscle tension, and sleep disorders. Rohypnol is a very powerful sedative that can last up to 12 hours, with some residual effects lasting as long as 24 hours. Rohypnol is 10 times more potent than the most commonly known benzodiazepine, Valium (Figure 2.1). 

The effects of GHB on sleep have been well documented. Even small doses produce relaxation, tranquillity, and drowsiness. A sufficiently high dose of GHB will induce sudden sleep within 5 to 10 minutes. Although other sedative-hypnotics interfere with various stages of the sleep cycle and prevent the body from achieving complete and balanced rest, GHB-induced sleep seems to closely resemble normal physiological sleep.42 In a clinical study, GHB has been shown to induce sleep rapidly without suppressing REM sleep, thereby improving sleep quality.43... 

This large category of depressants comprises alcohol "sleeping pills/ and certain tranquilizers. In low doses these drugs promote relaxation and restfulness (sedation), especially in the daytime. Larger doses, especially at night, induce sleep (the word hypnosis comes from the name of the Greek god of sleep). "Sedative-hypnotic" refers to this double action. 

The pharmaceutical industry has tried hard to convince doctors and patients that these chemicals arc revolutionary drugs that specifically reduce anxiety, making people calm and relaxed. In fact, the minor tranquilizers are just another variation on the theme of alcohol and other sedative-hypnotics, with the same tendency to produce adverse effects and dependence. 

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