Thomas G. Waddell Hal J o n e s and A. Lane Keith Universitv of Tennessee at Chattanooaa Chattanooga. TN 37402
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Legendary Chemical Aphrodisiacs
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Currently, the great scientific quests of man include such monumental problems as the harnessing of fusion energy, the curing of cancer, and the understanding and slowing of the aging process. Lying as an undercurrent beneath these and other &eat ouests has been another long-standine interest, often Yhighliihted, but more commonly whispered between conceots in the chemical and medical literature. The search for aithentic chemical aphrodisiacs has drawn the interest of established scholars ( I ) and students (most often undergraduates). Dorland's "Illust~atedMedical Dictionary" defines an aphrodisiac as "any drug that arouses the sexual instinct." Armed with this definition, we have surveyed the literature and have collected here information and references regarding this topic from a chemist's perspective. To our knowledge, such a review has not previously appeared. The nresent survev is not comorehensive, nor could i t easily he, since references to aphrodisiacs appear from many disci&nes throuehout recorded time. Instead, this paper includes some outst&ding substances of either legendary repute or scientific interest. For cunvenienw of discussion the ampounds are gmuped as plant natural products, animnl natural products, and synthetic products. Plant Natural Products One of the more well-known plant natural products with reported aphrodisiac activity is the indole alkaloid yohimhine (I), derived from the bark of the West African tree Corynanthe yohimbe (2). Yohimbine has been used to treat impotence in humans and as a sexual stimulant for horses, cattle, sheep, and dogs (3). Although this reported use for yohimhine may he related to its action as a central nervous system stimulant. there is little convincing- evidence for such an aphrodisiac effect (4). The infamous poison strychnine (11) is also an indole alkaloid, obtained chiefly from Nux Vomica and from other
seeds and plants of the genus Strychnos. Strychnine salts have been used as tonics in convalescence from illness, in alcoholism, in diminished vision, and in sexual impotency (5). However, a more recent cumment 14) un the therapeutic use of this danrtmna toxin seriously challenges the legitimacy of strychnine's medical applicatiok since only toxic doses seem to elicit desirable biological responses. An East African tree (eenus Xvlocarous). widelv used in folk medicine, has yielde&anothe; substancLof interest. The rioe fruits of this tree are sweet. hut the unrine ones are hitter. and it is the latter fruit which carries an aphrodisiac reputa: tion. The hitter principle of unripe Xylocarpus is an indole alkaloid precursor, xylomollin (111). In nature, xylomollin repels insect predators, and in rat liver mitochondria it inhiiit9 respiration ( 6 ) .In humans, any aphrndisiac effect of xvli~molli~~ has not heen established. A recenrlv ouhlished herhal handbook 171 describes vanilla as a ". . . well-known flavoring substance which has unquestionable aohrodisiac oualities." In addition. this reference remarks that the quantities found in ice cream are hardly enoueh for results and warns that hieh doses are toxic. Thus. the constituents of vanilla lure the chemist's interest. plants of the genus Vanilla (Orchid Family) are found in the damp forests of eastern Mexico and Tahiti. In addition to a major constituent, vanillin (IV), Bohnsack has reported (8)the occurrence in Bourbon vanilla of acetaldehyde, diacetyl, furfural, 2,5-dimethylfurfural, anisaldehyde, henzaldehyde, acetophenone, along with acetic, isobutyric, isovaleric, henzoic, auisic, and vanillic acids. Other flavoring agents smack of legend. Licorice has been in use as a medicinal since ancient times. I t is mentioned by Theophrastus and Dioscorides and by the Roman writers Marcellus and Pliny and was common in Europe during the Middle Ages (5). Licorice root, Glycyrrhiza glabra, was made into a tea by ancient Hindus to increase sexual vigor (7). This nlant contains un to 11%elvcvrrhizic acid (V). . .. an intenselv sweet, water soluble, triterpene glycoside, known for its anti-inflammatow. ,. anti-allereic. .. . antise~tic. . .and corticosteroid rffect.; ( 9 ) . The flavanoids liquiritin, liquiritigenin, isoliquiritin, and isuliquiritigrnin haw bern i s h t e d from Spanish G1)c)rrhizu (10). Wise men ofnncient times torhnde the use of wild mint [Mrnlho species, by wldiers in war hecause it ". . .aroused them rrnti(nllg and took away their animosity and courage to fight" 171. This familiar plant is rich in volatile monoteroenes. mainlv menthol I V I and ~ includinr menthnne. menthyl acetate, limonene, camphene, and alpha and betaoinene (11 ). In thd southeastern United States, hunters prowl the forests in search of American einsene. Panax uuinuuefolium, as inis weliestablished. F& over deed, the reputation ofthis 5000 vears. Oriental men have consumed einsene root daily to retain their virility (12-23). A recent re;iew (14) catalogs the chemical composition of ginseng roots. The most important group of biologically active substances are D-glucosides, in which the aglucon portion is a triterpene (cf. \I)such as protopenaxedi& prot&penaxetriol,or oieanolic acid. Among other substances occurring in this plant are steroids, -peptides, sugars, and vitamins. I t has been stated that the aphrodisiac nature of marijuana has been recognized for many centuries. But is this a specific effect or might the marijuana constituents act as wine and soft A.
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one can speculate that, perhaps, in man's distant past, when hygiene and current social pressures were unknown, true aphrodisiacs (these aliphatic acids) were expressed. Other human secretions, the skin lipids, may be latent aphrodisiacs. Nicolaides has listed (23) the unusual lipids occurring on the surface of human skin. Among these (squalene, sterols, wax esters, acyl glycerols, fatty acids) is farnesol (IX), a Cis sesquiterpene alcohol used industrially as a perfume and presumably of some value in human sexual attraction. Synthetic Products In a paper entitled "Aphrodisiac Effect of p-Chlorophenylalanine," Gessa coworkers presented and referred to evidence that this haloeenated amino acid increases the sexual performance of male rats when the experimental subjects are chosen from sexually sluggish animals (24). Of more relemnce to bumnnsis thv recent case of hromocryptine (X)(2FiJ.Hromocrsotine is a synthetic nerivariw of the errot alkaloids, a group bf natural broducts produced by a fungus. In clinical trials, treatment with X has restored sexual desire and potency to patients so lacking. I t was concluded that hromocryptine acts to lower prolactin levels, which are known to inhibit synthesis of male hormones.
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music do to mellow inhibitions? Even the aphrodisiac enthusiasts allow this question (14). Whatever may he the truth, the chemical constitution of this widely-used drug must be mentioned in this discussion. Plants of the genus Cannabis are grown in temperate countries for their fibers (hemp) and fruits (hemp seed). Cannabis foliage leaves and twigs, when dried, constitute the drug known as marijuana (15). The chemistry and pharmacology of this plant have been studied extensively (16). The active constituents are cannahinoids, with structures related to the famous main ingredient, tetrahvdrocannahinol (VIII) . . (17). . . , A complete list of plants with legendary aphrodisiar properties is much loneer than can he oresented in this o a ~ e (7). r Mercifully, the scyentificallyinteiesting animal prod&ts rum o d to have these effects are fewer. ~~~
Conclusion This brief discussion and collection of human chemical aphrodisiacs has progressed from unfounded legend (yobimhine), throueh scientific oossihility (aliphatic acids), to medical value (hromocryptine). The long search for a true and available aphrodisiac continues. Few topics can rival the interest generated by compounds that arouse sexual instinct.
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Cantharides (Spanish flies) consist of the dried insects, Cantharis uesicatoria. The active irritant in the crude drug is cantharidin (VIII) (181, a compound which exerts a vesicant action on the skin and mucous membranes. When taken internally it causes vomiting, abdominal pain, and shock. Due to an irritation of the urethra, priapism may result. Therefore, the reputation of Spanish fly as an aphrodisiac is widely acits use, in this way, is dangerous and often .cepted. . . ..However, -, lethal ( l Y ) . An equally famous legendary substance of animal is the rhinoceros horn which in powder form was once widely spoken of in Asian countries as a treatment for fever, as a general antidote, and as an aphrodisiac. ~h~ ,.hemica] constituents of the rhinoceros horn have been determined by Inagaki and Oida (20)' Polypeptides' sugar' phosphorous' and ethanolamine are present along with the free amino acids aspartic acid, glutamic acid, cysteic acid, threonine, serifie, ~roline,glyciue, alanine, valine, methionine, cystine, i s o h cine, leucine, ornithine, lysine, histidine, and arginine. Volatile aliphatic acids (acetic, propanoic, methylpropanoic, hutanoic, methylhutanoic, methylpentanoic) occur in the normal vaginal secretions of a wide range of primate species (21), including humans. These organic acids possess sex-attractant properties in monkeys and stimulate the sexual activity of males via olfactory pathways (22). The role of olfactory mechanisms in human sexual behavior is not clear, hut
342 1 Journal of Chemlcal Education
One of us (T.G.W.) is grateful to his many organic chemistry students who continually and persistently ask questions regarding this topic. Literature CHed Benedek,T. G., Bullefinal th~Xi&oryo/M~diiiii, 45.322 11971). Perrat, E..Hamet, R., BUN.Sci. Phormoeol., 39,593 (1932). Stecher, P. G., (Edilor)."The Merck Index." 8th Ed.. Merck and Co., 1968, p. 1125.,, ~ G m d L.~S.,~ Gilmsn. . A,, (Editom). "ThePharmacologieal h i s o f Therapeutics. 4th Ed.. The MacMillanCo..London. 1970.p. 561. (5) Youngken, H. W., "Textbaok of Pharmamgncsy,"6th Ed., ?heBlaldstonCo.. T m b , 1948, p. 668. (6) Meimxald. J.. PrestGch, G. D.. Nakankhi, K.. Kubo, I.. Science. 199.1167 (1978). (7) "Herbal Aphrodisiaea: Stone Kingdom Syndicate, San Rafael, Califania. 1971. P. 8. (8) Bohnaack. H..Riosclut. Ammen, Kaerp~rflegem.,17,133 (1967). (9) Muchnik, 2. S.,Rortit. Resw., 12.78 (1976). (10) vanH u l l e . C . . ~ ~ ~ ~ ~ k ~ ~ ~ , ~M . .. ~. P a n~ d~~~~~ o~dzo,~i8(1971). i.l ,l ~ , (11) Chsndra,V.,Singh,A.,Kapmr,L.D.,IndianParlum..16,41(1971). (12) Y~wk~n.H.W.."TytbmkofPhanosmgnce~."6thEd..ThcB~8tonCo.,TOm~. 1948,~.608. (13) . - H ~~ ~~ h~ ~ ~d iI~ i a cstone s . ' . ~ i n g syndicate, d ~ ~ sao &fad. cdifomia, 1971, p. 4. (14) "Herbal Aphrodisiacs..' Stone Kingdom Syndioate, San &fwl, California. 1971, 7. (15) Youogkeo,H.W.,'Textbookof~harmamgnaey~6th~d.,na~1alriaton~o.,~mnto, 1948,~.276. (16) ~ ~J. D.P.,~ ti,n. M. h F..conmbi. ~ ~ H~BI~I,, .143 (1976). (17) ~ ~ ~ ~ i , ~ . , ~ e e h o u ~A a~ m~ them , F~ .. , .so
