Eucaine

The bicyclic tropane ring of cocaine of course presented serious synthetic difficulties. In one attempt to find an appropriate substitute for this structural unit, a piperidine was prepared that contained methyl groups at the point of attachment of the deleted ring. Condensation of acetone with ammonia affords the piperidone, 17. Isophorone (15) may well be an intermediate in this process conjugate addition of ammonia would then give the aminoketone, 16. Further aldol reaction followed by ammonolysis would afford the observed product. Hydrogenation of the piperidone (18) followed then by reaction with benzoyl chloride gives the ester, 19. Ethanolysis of the nitrile (20) affords alpha-eucaine (21), an effective, albeit somewhat toxic, local anesthetic. 

Allobarbital, 269 Allopurinol, 152, 426, 427 Allylestrenol, 172 Aloxidone, 232 Alpha eucaine, 8 Alphaprodine, 303, 304, 305 Alprenolol, 117 Althizide, 359 Ambucaine, 11 Ambucetamide, 94 Amidoquine, 342 Amiloride, 278 Aminitrazole, 247 7-Aminocephalosporanic acid (7-ACA), 416, 417 Aminoglutethemide, 257... 

Beckmann rearrangement, 157 Bemidone, 305 Bemigride, 258 Benactizine, 93 Benadryl , 41 Bendroflumethiazide, 358 Benzamphetamine, 70 Benzestrol, 103 Benziodarone, 313, 314 Benzocaine, 9 1,4-Benzodioxans, 352 Benzguinamide, 350 Benzydamine, 323 Benzylpenicillin, 408, 409, 410 Bergstrom, Sune, 24 Beta eucaine, 9 Betamethosone, 198 Bethanidine, 55 Bhang, 394... 

Cocaine produces vasoconstriction (blanching) probably by sensitizing to sympathetic stimulation. This action is lacking in the other local anesthetics. Procaine has practically no vascular effect alypin, eucaine, and stovaine cause some dilatation. Cocaine decreases capillary hemorrhage procaine, apothesine, and other synthetic anesthetics tend rather to increase bleeding. 

Anesthesia from intact surfaces requires that the drug must be absorbable. This excludes the intact skin. Cocaine, butyn, metycaine, and diothane are readily absorbed from mucous membranes, and are therefore efficient but also correspondingly toxic. Procaine and apothesine are relatively inabsorbable and therefore less applicable. Alypin and [3-eucaine are intermediate, but the order of absorbability varies for different mucosae. 

The Chemistry Department of the University of Sheffield was one of the major participants in organic synthesis (see Chap. 5). William Palmer Wynne assembled a team of six women chemists, including Emily Turner, Dorothy Bennett, and Annie Mathews, to synthesise P-eucaine.15 However, the most noteworthy production was that at Imperial College, in the group run by Martha Whiteley (see Chap. 3).16 Whiteley s seven assistants were all women and included Frances Micklethwait (see Chap. 3), who received an M.B.E. for her contributions to the war effort.17... 

This compound possesses anesthetic properties and is less toxic than cocaine. It is irritating when injected into the body and is now replaced by beta-eucaine which is a similar compound derived from acetaldehyde di-acetone amine, vinyl di-acetone amine. 

Stovaine. Al5rpine.—This study of cocaine and eucaine led to the examination of other compounds containing an alcohoUamine ester grouping, similar to that present in these anesthetics. The formula for cocaine contains the following grouping ... 

Figure 20-2 The incorrect structures proposed for cocaine (a) and tropine (b) by Albert Einhorn and Georg Merling. Structures of methyltrlacetone alkamine (c). alpha-Eucaine (d). and beta-Eucaine (e).

Eucaine. 2,2,6-Trimelhyl-4-piperidinol benzoate (ester) a-4-benzoyl oxy-2,2,6-trimethy] pi peri dine a-vinyl-diacetonalkamine benzoate benzatnine betacaine eucaine B. CjjHjjNOj mol wt 247.33. C 72.84%, H 8.56%, N 5.66%, O 12,94%. Prepn from lower melting form (a-form) of 2,2,6-trimethyl-4-piperidino[ and benzoyl chloride Harries, Ann. 417, 107, see p 175 (1918). Stereochemistry King, J. Chem. Soc. 125, 41 (1924) Stenlake. J. Pharm. Pharmacol 6, 164 (1954). Configuration Perks, Russell, ibid. 19, 3 8 (1966). 

Eucaine A and Eucaine B were the first of the synthetic compounds to come into general use. These are related to open-chain compounds of... 

Potassium acts as a powerful synergist for local anesthetics under some conditions (59-62). The anesthetic effect of cocaine and /3-eucaine on the sensory and motor endings of the frog sciatic and on the sensory nerve of frog and guinea pig skin and the action of novocaine on the sensory nerve is considerably enhanced by potassium. The skin anesthesia produced by potassium chloride is intensified by minute quantities of cocaine, d-eucaine,... 

In 1896 and 1897 Eucaine A and Eucaine B were prepared and came into general use as a result of their potent action. These compounds indicated that the entire condensed ring system of cocaine was not necessary for activity. The common denominator in all of the compounds so far found active was that they were amino esters. Shortly after 1900 Einhorn foimd that alkyl esters of p-aminobenzoic acid were active anesthetics, and a little later he found that the dialkylaminoalkyl esters were more active... 

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