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November 11, 1992, Vol 268, No. 18 >
ARTICLE | November 11, 1992

Tacrine for Treating Alzheimer's Disease FREE

Gary W. Small, MD
[+] Author Affiliations

The views expressed are those of the author and do not necessarily represent those of the Department of Veterans Affairs.

Repint requests to UCLA Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024-1759 (Dr Small).


JAMA. 1992;268(18):2564-2565. doi:10.1001/jama.1992.03490180096034
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References

Tacrine (tetrahydroaminoacridine, THA) was first available in Australia in the mid 1940s when it was used with morphine to lessen respiratory depression without affecting analgesia.1 Its anticholinesterase activity eventually led to clinical trials in patients with presumptive Alzheimer's disease (AD), but these pilot studies demonstrated only modest efficacy using tacrine alone2 or in combination with lecithin.3 Consistent findings of a cholinergic deficit in AD make such cholinergic manipulation a theoretically attractive palliative treatment. Trials of other cholinomimetics, however, had shown at best modest results and often practical limitations—eg, choline causes a fishy skin odor and the 30-minute half-life of physostigmine is too brief for lasting clinical effects.

See also p 2523.

Scientific and public interest, as well as controversy, exploded in 1986 when Summers and colleagues4 reported dramatic results from a double-blind, placebo-controlled trial of tacrine in 17 patients with apparent clinical diagnoses of AD. One

REFERENCES

1 +
Shaw FH, Bentley G.  Some aspects of the pharmacology of morphine, with special reference to its antagonism by 5-amino-acridine and other chemically related compounds. Med J Aust . 1949;;2:868-874.
2 +
Summers WK, Viesselman JO, Marsh GM, Candelora K.  Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biol Psychiatry . 1981;;16: 145-153.
3 +
Kaye WH, Sitaram N, Weingartner H, et al.  Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biol Psychiatry . 1982;;17:275-280.
4 +
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A.  Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med . 1986;;315:1241-1245.
5 +
Division of Neuropharmacological Drug Products, Food and Drug Administration.  Tacrine as a treatment for Alzheimer's dementia: an interim report from the FDA. N Engl J Med . 1991;;324:349-352.
6 +
Chatellier G, Lacomblez L,  on behalf of Groupe Francais d'Etude de la Tetrahydroaminoacridine. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. BMJ . 1990;;300:495-499.
7 +
Gauthier S, Bouchard R, Lamontagne A, et al.  Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease: results of a Canadian double-blind, crossover, multicenter study. N Engl J Med . 1990;; 322:1272-1276.
8 +
Farlow M, Gracon SI, Hershey LA, et al.  A controlled trial of tacrine in Alzheimer's disease. JAMA . 1992;;268:2523-2529.
9 +
Davis KL, Thai LJ, Gamzu E, et al.  Tacrine in patients with Alzheimer's disease: a double-blind placebo-controlled multicenter study. N Engl J Med . In press.
10 +
Eagger SA, Levy R, Sahakian BJ.  Tacrine in Alzheimer's disease . Lancet . 1991;; 337:989-992.
11 +
Folstein M, Folstein S, McHugh P.  The Mini-Mental State Examination. Psychiatry Res . 1975;;12:189-198.
12 +
Schneider LS.  Tetrahydroaminoacridine and lecithin for Alzheimer's disease. N Engl J Med . 1990;;323:919-920.
13 +
Wilcock GK, Murray JR, Blakemore CB, et al.  Tacrine and lecithin in Alzheimer's disease. BMJ . 1990;;300:939-940.
14 +
Jarvik LF, Berg L, Bartus R, et al.  Clinical drug trials in Alzheimer disease: what are some of the issues? Alzheimer Dis Assoc Disord . 1990;;4:193-202.
15 +
Bondareff W, Mountjoy CQ, Roth M, et al.  Age and histopathologic heterogeneity in Alzheimer's disease: evidence for subtypes. Arch Gen Psychiatry . 1987;;44: 412-417.
16 +
Reinikainen KJ, Paljarvi L, Halonen T, et al.  Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease. Neurobiol Aging . 1987;;9:245-252.
17 +
Drukarch B, Kits KS, Van der Meer EG, et al.  9-amino 1,2,3,4- tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer's disease, inhibits acetylcholinesterase activity and slow outward K+ current. Eur J Pharmacol . 1987;;141:153-157.
18 +
Stevens DR, Cotman CW.  Excitatory actions of tetrahydro-9-aminoacridine (THA) on hippocampal pyramidal neurons. Neurosci Lett . 1987;;79:301-305.
19 +
Farrer LA, Myers RH, Cupples LA, et al.  Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology . 1990;; 40:395-403.
20 +
Small GW, Leuchter A, Mandelkern MA, et al.  Clinical, neuroimaging, and environmental risk differences in monozygotic female twins appearing discordant for dementia of the Alzheimer type. Arch Neurol . In press.
21 +
Schneider LS.  Clinical pharmacology of aminoacridines in Alzheimer's disease. Neurology . In press.

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1 +
Shaw FH, Bentley G.  Some aspects of the pharmacology of morphine, with special reference to its antagonism by 5-amino-acridine and other chemically related compounds. Med J Aust . 1949;;2:868-874.
2 +
Summers WK, Viesselman JO, Marsh GM, Candelora K.  Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biol Psychiatry . 1981;;16: 145-153.
3 +
Kaye WH, Sitaram N, Weingartner H, et al.  Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biol Psychiatry . 1982;;17:275-280.
4 +
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A.  Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med . 1986;;315:1241-1245.
5 +
Division of Neuropharmacological Drug Products, Food and Drug Administration.  Tacrine as a treatment for Alzheimer's dementia: an interim report from the FDA. N Engl J Med . 1991;;324:349-352.
6 +
Chatellier G, Lacomblez L,  on behalf of Groupe Francais d'Etude de la Tetrahydroaminoacridine. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. BMJ . 1990;;300:495-499.
7 +
Gauthier S, Bouchard R, Lamontagne A, et al.  Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease: results of a Canadian double-blind, crossover, multicenter study. N Engl J Med . 1990;; 322:1272-1276.
8 +
Farlow M, Gracon SI, Hershey LA, et al.  A controlled trial of tacrine in Alzheimer's disease. JAMA . 1992;;268:2523-2529.
9 +
Davis KL, Thai LJ, Gamzu E, et al.  Tacrine in patients with Alzheimer's disease: a double-blind placebo-controlled multicenter study. N Engl J Med . In press.
10 +
Eagger SA, Levy R, Sahakian BJ.  Tacrine in Alzheimer's disease . Lancet . 1991;; 337:989-992.
11 +
Folstein M, Folstein S, McHugh P.  The Mini-Mental State Examination. Psychiatry Res . 1975;;12:189-198.
12 +
Schneider LS.  Tetrahydroaminoacridine and lecithin for Alzheimer's disease. N Engl J Med . 1990;;323:919-920.
13 +
Wilcock GK, Murray JR, Blakemore CB, et al.  Tacrine and lecithin in Alzheimer's disease. BMJ . 1990;;300:939-940.
14 +
Jarvik LF, Berg L, Bartus R, et al.  Clinical drug trials in Alzheimer disease: what are some of the issues? Alzheimer Dis Assoc Disord . 1990;;4:193-202.
15 +
Bondareff W, Mountjoy CQ, Roth M, et al.  Age and histopathologic heterogeneity in Alzheimer's disease: evidence for subtypes. Arch Gen Psychiatry . 1987;;44: 412-417.
16 +
Reinikainen KJ, Paljarvi L, Halonen T, et al.  Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease. Neurobiol Aging . 1987;;9:245-252.
17 +
Drukarch B, Kits KS, Van der Meer EG, et al.  9-amino 1,2,3,4- tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer's disease, inhibits acetylcholinesterase activity and slow outward K+ current. Eur J Pharmacol . 1987;;141:153-157.
18 +
Stevens DR, Cotman CW.  Excitatory actions of tetrahydro-9-aminoacridine (THA) on hippocampal pyramidal neurons. Neurosci Lett . 1987;;79:301-305.
19 +
Farrer LA, Myers RH, Cupples LA, et al.  Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology . 1990;; 40:395-403.
20 +
Small GW, Leuchter A, Mandelkern MA, et al.  Clinical, neuroimaging, and environmental risk differences in monozygotic female twins appearing discordant for dementia of the Alzheimer type. Arch Neurol . In press.
21 +
Schneider LS.  Clinical pharmacology of aminoacridines in Alzheimer's disease. Neurology . In press.

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