50 – 65. Earlier reviews: 1999, 16, 199 – 208; 1997, 14, 359 – 372. This is produced in exactly the same way

398 ALKALOIDS Continued and is a valuable pharmacological tool for the study of this process. Saxitoxin and tetrodotoxin below are some of the most potent non-protein neurotoxins known, and are active at very low concentrations µ g kg − 1 . Tetrodotoxin Tetrodotoxin Figure 6.136 is traditionally associated with the puffer fish, Tetraodon species, a fish known as fugu, a highly prized delicacy eaten in Japan. Preparation of fugu is a skilled operation in which organs containing the highest levels of toxin, e.g. liver, ovaries, and testes, are carefully separated from the flesh. Even so, deaths from fugu poisoning are not uncommon, and the element of risk presumably heightens culinary appreciation of the fish. As with saxitoxin, tetrodotoxin appears to be produced by microorganisms, and symbiotic marine bacteria, e.g. Vibrio species, have been implicated as the synthesizers. In addition to fugu, several other species of fish, newts, and frogs have been found to accumulate tetrodotoxin or related structures. The mode of action of tetrodotoxin is exactly the same as that of saxitoxin above, though there are some subtle differences in the mechanism of binding. FURTHER READING Biosynthesis, General Dalton DR 1991 Alkaloids. Kirk–Othmer Encyclope- dia of Chemical Technology , 4th edn, Vol 1. Wiley, New York, pp 1039 – 1087. Herbert RB 2001 The biosynthesis of plant alkaloids and nitrogenous microbial metabolites. Nat Prod Rep

18, 50 – 65. Earlier reviews: 1999, 16, 199 – 208; 1997, 14, 359 – 372.

Kutchan TM 1995 Alkaloid biosynthesis – the basis for metabolic engineering of medicinal plants. Plant Cell 7 , 1059 – 1070. Kutchan TM 1998 Molecular genetics of plant alkaloid biosynthesis. The Alkaloids, Chemistry and Phar- macology ed Cordell GA Vol 50. Academic, San Diego, pp 257 – 316. Misra N, Luthra R, Singh KL and Kumar S 1999 Recent advances in biosynthesis of alkaloids. Com- prehensive Natural Products Chemistry , Vol 4. Else- vier, Amsterdam, pp 25 – 59. Tropane Alkaloids Bernstein PR 1992 Antiasthmatic agents. Kirk–Othmer Encyclopedia of Chemical Technology , 4th edn, Vol 2. Wiley, New York, pp 830 – 854. Evans WC 1990 Datura, a commercial source of hyoscine. Pharm J 244, 651 – 653. Griffin WJ and Lin GD 2000 Chemotaxonomy and geographical distribution of tropane alkaloids. Phy- tochemistry 53 , 623 – 637. Gritsanapan W and Griffin WJ 1992 Alkaloids and metabolism in a Duboisia hybrid. Phytochemistry 31, 471 – 477. Lounasmaa M and Tamminen T 1993 The tropane alkaloids. The Alkaloids, Chemistry and Pharmacol- ogy ed Cordell GA Vol 44. Academic, San Diego, 1 – 114. Molyneux RJ, Nash RJ and Asano N 1996 Chemistry and biological activity of the calystegines and related nortropane alkaloids. Alkaloids, Chemical and Bio- logical Perspectives ed Pelletier SW Vol 11. Else- vier, Amsterdam, pp 303 – 343. O’Hagan D 2000 Pyrrole, pyrrolidine, pyridine, piperi- dine and tropane alkaloids. Nat Prod Rep 17, 435 – 446. Earlier review: 1997, 14, 637 – 651. O’Hagan D and Robins RJ 1998 Tropic acid ester biosynthesis in Datura stramonium and related species. Chem Soc Rev 27, 207 – 212. Cocaine Johnson EL and Emcho SD 1994 Variation in alkaloid content in Erythroxylum coca leaves from leaf bud to leaf drop. Ann Bot 73, 645 – 650. Lenz GR, Schoepke HG and Spaulding TC 1992 Anes- thetics. Kirk–Othmer Encyclopedia of Chemical Tech- nology , 4th edn, Vol 2. Wiley, New York, 778– 800. FURTHER READING 399 Singh S 2000 Chemistry, design, and structure– activity relationship of cocaine antagonists. Chem Rev 100, 925 – 1024. Woolverton WL and Johnson KM 1992 Neurobiology of cocaine abuse. Trends in Pharmacological Sci- ences 13 , 193 – 200. Epibatidine Daly JW, Garaffo HM, Spande TF, Decker MW, Sulli- van JP and Williams M 2000 Alkaloids from frog skin: the discovery of epibatidine and the potential for developing novel non-opioid analgesics. Nat Prod Rep 17 , 131 – 135. Szantay C, Kardos-Balogh Z and Szantay C Jr 1995 Epibatidine. The Alkaloids, Chemistry and Phar- macology ed Cordell GA Vol 46. Academic, San Diego, pp 95 – 125. Pyrrolizidine Alkaloids Hartmann T 1999 Chemical ecology of pyrrolizidine alkaloids. Planta 207, 483 – 495. Hartmann T and Witte L 1995 Chemistry, biology and chemoecology of the pyrrolizidine alkaloids. Alkaloids, Chemical and Biological Perspectives ed Pelletier SW Vol 9. Wiley, New York, 155– 233. Liddell JR 2000 Pyrrolizidine alkaloids. Nat Prod Rep

17, 455 – 462. Earlier reviews: 1999, 16, 499 – 507; 1998, 15, 363 – 370.