Narcissus and Daffodil

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Clinical trials of galanthamine 365 good indicator of 3-year outcome. No clinically significant disturbances in blood biochemistry or liver function tests were observed. SUMMARY The results of early trials of galanthamine compare well with those of later studies, but one should remember that today’s criteria for classification of patients with AD are much more precise. It has been estimated that early inclusion criteria may have been only 85% specific for AD (Wade et al., 1987). Most of the early studies reported here are really no more than pilots, and leave much to be desired; however, they were conducted by three, independent research groups and the results attracted sufficient attention to prime the planning of more extensive and sophisticated trials. Such trials are at present ongoing and results have not yet been published. One reason why the anticholinesterase approach is only partially successful in AD is the multifactorial nature of the neuropharmacological deficits seen in the disease (Perry, 1987). As AD appears to be a disorder involving deficits in a number of neurotransmitters, it seems logical to assume, and on the basis of the evidence, correct, that the strategy of acetylcholine preservation slows the progression of the disease but does not halt it. Secondly, a multifactorial approach, involving several pharamcological interventions at once (for example, combined strategies to boost levels of noradrenaline, serotonin, gamma-aminobutyric acid, somatostain and corticotrophin releasing factor, all of which have been shown to be deficient in AD), may hold more promise. From the trial data so far, it would appear that there is a sub-group of patients who respond well to galanthamine, and in whom the cholinergic deficit is a major component of their disease. The side effect profile of galanthamine appears favourable, particularly when compared with tacrine, where hepatotoxicity is a particular worry (Knapp et al., 1994; Wagstaff and McTavish, 1994) and metrifonate, where clinical trials have recently been suspended because of concerns about muscle weakness (personal communication, Bayer UK). Anticholinergic side effects, particularly nausea and vomiting, may be a problem, and measures to minimise these, such as slow upward titration of the initial dose and co-administration of antiemetics, should be investigated further. Galanthamine is approved by the Austrian authorities for use in AD. However, there remains at present a lack of controlled, double-blind trials of sufficient quality and length to define clearly the role of this interesting agent. Head-to-head comparisons with other agents such as tacrine have not been performed, and more information is also required on long-term use, dose response, use in old age (where renal and hepatic impairment are common), and potential interactions with other drugs used in co-morbid conditions (such as Parkinson’s disease, agitation, anxiety, aggression and depression). In terms of pharmaceutical development, a once-daily dosage form would be a useful advance, having obvious applications in elderly or forgetful patients and at least one transdermal, controlled release patch is under development (Morierty, 1995). An alternative is to synthesise galanthamine analogues with extended halflife and improved efficacy.
366 D. Brown REFERENCES Bartus, B.T., Dean, R.L. and Beer, B. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science, 217, 408–417. Bartus, B.T., Dean, R.L., Pontecorvo, M.J. and Flicker, C. (1985) The cholinergic hypothesis: a historical overview, current perspectives and future directions. Annals of the New York Academy of Science, 444, 332–358. Berzewski, H., Kewitz, H. and Dans, B. (1994) Galanthamine, a selective nontoxic centrally acting and reversible acetylcholinesterase inhibitor for the treatment of SDAT. 19th Colloquium of the College of International Neuropsychopharmacology Congress, 27 June –1 July 1994, Washington D.C. Coyle, J.T., Price, C.L. and DeLong, M.R. (1983) Alzheimer’s disease: a disorder of cholinergic innervation. Science, 219, 1184–1190. Crow, T.J. and Grove-White, I.G. (1973) An analysis of the learning deficit following hyoscine administration to man. British Journal of Pharmacology, 49, 322–327. Dal-Bianco, P., Maly, J., Wober, C., Lind, C., Koch, G., Hufgard, J., Marschall, I., Mraz, M. and Deecke, L. (1991) Galanthamine treatment in Alzheimer’s disease. Journal of Neural Transmission, 33, 59–63. Davies, P. (1983) The neurochemistry of Alzheimer’s disease and senile dementia. Medical Research Review, 3, 221–236. Davies, P. and Maloney, A.J. (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet, 2, 1400–1405. Davies, P. and Powchik, P. (1995) Tacrine. Lancet, 345, 625–630. Folstein, M.F., Folstein, M.E. and McHugh, P.R. (1975) Mini-mental State. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. Geaney, D.P., Soper, N., Shepstone, B.J. and Cowen, P.J. (1990) Effect of central cholinergic stimulation on regional cerebral bloodflow in Alzheimer disease. Lancet, 335, 1484– 1487. Giacobini, E., Mori, F. and Lai, C.C. (1996) The effect of cholinesterase inhibitors on the secretion of APPs from rat brain cortex. Annals of the New York Academy of Science, 777, 393–398. Gray, A. and Fenn, P. (1993) Alzheimer’s disease: the burden of the illness in England. Health Trends, 25, 31–37. Gruber, R.P., Stone, G.C. and Reed, D.R. (1967) Scopolamine-induced anterograde amnesia. International Journal of Neuropharmacology, 6 (3), 187–190. Jann, H.W. (1998) Pharmacology and clinical efficacy of cholinesterase inhibitors. American Journal of Health Systems Pharmacy, 1 (55), S22–25. Jorm, A.F., Korten, A.E. and Jacomb, P.A. (1991) Projected increases in the number of dementia cases for 29 developed countries: application of a new method for making projections. Acta Psychiatrica Scandinavica, 78, 493–500. Kewitz, H., Berzewski, H., Rainer, M., Dal-Bianco, P., Friedl, E., Deisenhammer, J.E., Kummer, J., Uebelhack, R., Engel, R., Lee, C. and Hartung, U. (1994) Galanthamine, a selective nontoxic acetylcholinesterase inhibitor is significantly superior over placebo in the treatment of SDAT. Abstract No. P58–147. Neuropsychopharmacology, 10(3S), 130S. Knapp, M.J., Gracon, S.I., Davis, C.S., Solomon, P.R., Pendlebury, W.W. and Knopman, D.S. (1994) Efficacy and safety of high-dose tacrine: a 30-week evaluation. Alzheimer’s Disease and Associated Disorders, 8 (2S), S22-S31. McKhann, G., Drachman, E. and Folstein, M. (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 43 (7), 939–944.
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Narcissus and Daffodil
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Narcissus and Daffodil The genus Na
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Contents Preface to the series vii
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Preface to the series There is incr
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Preface My interest in flower-bulb
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Acknowledgements I would like to th
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Gordon R. Hanks Crop and Weed Scien
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Figures 1.1 The effect of bulb stor
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Figures/Plates xvii 7.8 Accumulatio
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Figures/Plates of different segment
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2 G.R. Hanks Information about the
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4 G.R. Hanks (1999), and the polysa
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3 2 4 1 1 3 2 4 5 Flowering in 1976
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8 G.R. Hanks Figure 1.6 Diagrammati
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10 G.R. Hanks (Rees, 1969). When fl
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12 G.R. Hanks Figure 1.8 The relati
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14 G.R. Hanks root system of commer
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16 G.R. Hanks Cremer, M.C., Beijer,
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18 G.R. Hanks Roh, S.M. and Lee, J.
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20 A.C. Dweck Figure 2.1 The narcis
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22 A.C. Dweck Julians Hertfordshire
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24 A.C. Dweck Herefordshire, if daf
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26 A.C. Dweck the basis of an ancie
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28 A.C. Dweck Britten, J. and Holla
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3 Classification of the genus Narci
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(1) (2) (3)
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34 B. Mathew d. Section Jonquillae
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36 B. Mathew N. cyclamineus DC. Flo
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38 B. Mathew 1c. Section Ganymedes
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40 B. Mathew umbel, fragrant; peria
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42 B. Mathew recognition whatsoever
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44 B. Mathew Note: N. elegans shows
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46 B. Mathew ssp. praecox Gatt. and
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(1) (2) (3) (4)
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50 B. Mathew Table 3.1 Horticultura
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52 B. Mathew RHS (1958) The Classif
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54 G.R. Hanks grown for galanthamin
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56 G.R. Hanks such as drying stores
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Table 4.4 Areas of Narcissus cultiv
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60 G.R. Hanks Following planting in
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62 G.R. Hanks lost, resulting in th
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64 G.R. Hanks pathogen-tested nucle
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Figure 4.1 Mean monthly weather dat
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68 G.R. Hanks (as well as natural e
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70 G.R. Hanks compaction and its ef
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72 G.R. Hanks bulbs with base rot)
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74 G.R. Hanks Figure 4.3 Modern fro
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76 G.R. Hanks caution. Higher rates
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78 G.R. Hanks can also be prevented
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80 G.R. Hanks Figure 4.4 A typical
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82 G.R. Hanks Planting date The pra
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84 G.R. Hanks Hanks and Jones, 1986
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86 G.R. Hanks On sloping sites, gro
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88 G.R. Hanks Insecticide and nemat
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90 G.R. Hanks bulb growth, especial
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92 G.R. Hanks Figure 4.7 Changes in
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94 G.R. Hanks methods have been tes
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96 G.R. Hanks the boxes, exiting at
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98 G.R. Hanks usually collected in
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100 G.R. Hanks respond to ethylene
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102 G.R. Hanks using thiabendazole
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104 G.R. Hanks required for the eff
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106 G.R. Hanks and cross-cutting, s
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108 G.R. Hanks In practice, moulds
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110 G.R. Hanks that, with enterpris
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112 G.R. Hanks Balatková, V., Tupy
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114 G.R. Hanks (Narcissus pseudonar
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116 G.R. Hanks Flint, G.J. (1983) E
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118 G.R. Hanks Hanks, G.R. and Rees
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120 G.R. Hanks Khatib, K. al (1996)
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122 G.R. Hanks Luyten, I. (1935) Ve
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124 G.R. Hanks O’Neill, T.M., Man
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126 G.R. Hanks Ruamrungsri, S., Rua
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128 G.R. Hanks Thompson, P.A. (1977
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130 G.R. Hanks Williams, M. (1996)
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132 J.B. Briggs Table 5.1 Typical g
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134 J.B. Briggs Table 5.3 Actual gr
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136 J.B. Briggs Table 5.4 Actual co
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138 J.B. Briggs Table 5.5 Capital c
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140 J.B. Briggs ADAS (1987a) Narcis
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142 J. Bastida and F. Viladomat Fig
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Table 6.1 Narcissus alkaloid struct
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Table 6.1b Continued Alkaloid name
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Table 6.1d Tazettine type O O R1 R2
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Table 6.1f Continued MeO Alkaloid n
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Table 6.2 Continued Species* Alkalo
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162 J. Bastida and F. Viladomat Tab
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Table 6.3 Continued Alkaloid* Formu
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Table 6.3 Continued Alkaloid* Formu
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176 J. Bastida and F. Viladomat Tab
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178 J. Bastida and F. Viladomat Cri
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180 J. Bastida and F. Viladomat It
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184 J. Bastida and F. Viladomat is
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186 J. Bastida and F. Viladomat and
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Table 6.4 Continued Alkaloid Activi
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196 J. Bastida and F. Viladomat tac
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198 J. Bastida and F. Viladomat Ang
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200 J. Bastida and F. Viladomat Boi
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202 J. Bastida and F. Viladomat lyc
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204 J. Bastida and F. Viladomat Fug
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206 J. Bastida and F. Viladomat Han
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208 J. Bastida and F. Viladomat Kin
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210 J. Bastida and F. Viladomat of
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212 J. Bastida and F. Viladomat Sp
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214 J. Bastida and F. Viladomat Wil
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216 C. Codina and, consequently, hi
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218 C. Codina easily lost on transf
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220 C. Codina they might be more su
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222 C. Codina µ g/g FW µ g/g FW 3
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224 C. Codina Kinetin As observed i
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226 C. Codina Table 7.3 Total produ
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228 C. Codina Accumulation of alkal
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230 C. Codina Accumulation of alkal
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232 C. Codina Effect on growth and
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234 C. Codina mg/g DW mg/g DW 0.90
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236 C. Codina mg/g DW mg/g DW 1.4 1
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238 C. Codina mg/g DW mg/g DW 1.5 1
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240 C. Codina Hanks, G.R. and Jones
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8 Narcissus and other Amaryllidacea
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244 O.A. Cherkasov and O.N. Tolkach
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9 Studies on galanthamine extractio
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258 M. Kreh Table 9.1 Results of ga
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260 M. Kreh relation to the qualita
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262 M. Kreh Figure 9.3 Galanthamine
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264 M. Kreh 2.0 flower 2 1 3 4 0 10
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266 M. Kreh • High purity of the
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268 M. Kreh fraction of Narcissus
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H O MeO O MeO H H HO H (1) (3) + 2
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272 M. Kreh Gorinova, N.I., Atanass
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274 R.M. Moraes (Katz and Taneck, 1
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276 R.M. Moraes bulbs of many Narci
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278 R.M. Moraes Galanthamine conten
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280 R.M. Moraes Table 10.2 The effe
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282 R.M. Moraes years, a yield of 1
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284 R.M. Moraes Kosley, R.W., Jr.,
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11 Extraction and quantitative anal
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288 N.P.D. Nanayakkara and J.K. Bas
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Table 11.1 GC and HPLC procedures f
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Table 11.1 Continued References Det
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12 Synthesis of galanthamine and re
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306 V.N. Bulavka and O.N. Tolkachev
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Page 335 and 336: 314 V.N. Bulavka and O.N. Tolkachev
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Page 373 and 374: 352 D. Brown Furusawa, E., Lum, M.K
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Page 377 and 378: 356 D. Brown examination of a brain
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Page 383 and 384: 362 D. Brown statistically signific
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Page 389 and 390: 368 D. Brown Wilcock, G.K., Scott,
Page 391 and 392: 370 K. Ingkaninan, H. Irth and R. V
Page 401 and 402: 16 Narcissus lectins Els J.M. Van D
Page 403 and 404: 382 E.J.M. Van Damme and W.J. Peuma
Page 413 and 414: 17 Narcissus in perfumery HISTORY C
Page 415 and 416: 394 C. Remy Figure 17.2 Flower coll
Page 417 and 418: Figure 17.3 Narcissus flowers sprea
Page 419 and 420: 398 C. Remy CONCLUSION The use of n
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Page 427 and 428: 406 C.G. Julian and P.W. Bowers sym
Page 429 and 430: 19 Review of pharmaceutical patents
Page 431 and 432: 410 J.R. Murray to certain RNA viru
Page 433 and 434: 412 J.R. Murray occurs in a two-pha
Page 435 and 436: 414 J.R. Murray cognitive function
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416 J.R. Murray given at a time bet
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418 J.R. Murray Hofmannor, D., Mosc
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420 Index Backache, 403 Bacterial d
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422 Index Divisions (classification
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424 Index Leaf numbers, 11 Leaf sco
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426 Index Poet’s cultivars, 34 Po
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428 Index Subgenus (taxonomy); Ajax
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