THE OVERVIEW OF STUDIES ON HUPERZINE A: A NATURAL DRUG FOR THE TREATMENT OF ALZHEIMER’S DISEASE - Medicinal Chemistry of Bioactive Natural Products - page 172

4.8.4 Clinical Trials

Four clinical phase I studies involving 72 healthy elderly subjects have been per-
formed and have showed that administration of ZT-1 in humans seems to be safe
and well tolerated. The incidence of possibly drug-related adverse events, in parti-
cular nervous system and gastrointestinal symptoms, was similar to placebo for
doses up to 1.5 mg. An international multicenter phase II trial for dose finding
and efficacy assessment, in mild-to-moderate AD patients, is underway in 28 hos-
pitals in Europe.
The initial assessment of the potential of ZT-1 to improve cognition showed that
it could antagonize the cognitive impairment induced by scopolamine in healthy
elderly volunteers. The study was conducted according to a randomized, placebo
and positive-controlled, double-blind and crossover design. Donepezil was a posi-
tive internal control.
Overall, ZT-1 reduced the cognitive impairments produced by scopolamine on
tasks measuring attention, working memory, episodic secondary memory, and
eye-hand coordination. These findings suggest that ZT-1 may be an effective symp-
tomatic treatment for the cognitive deficits associated with AD.

ABBREVIATIONS

ACh acetylcholine

AChE acetylcholinesterase

AChEI acetylcholinesterase inhibitor

AD alzheimer's disease

Ab amyloid b-peptide

b.i.d. bis in die ( ¼ twice a day)

BuChE butyrylcholinesterase

ChE cholinesterase

ECG electrocardiogram

GABA g-amino-n-butyric acid

HA huperzine A

hAChE human AChE

HB huperzine B

HI hypoxic-ischemic

H. serrata Huperzia serrata (Thunb.) Trev.

i.g. intragastric

i.m. intramuscularly

i.p. intraperitoneally

i.v. intravenously

IC 50 50% inhibitory concentration

LTR long-term retrievel

MMSE Mini-Mental State Examination

NMDA N-methyl-D-aspartate