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Transmitter-replacement Therapy in Alzheimer's Disease Using Intracerebroventricular Infusions of Receptor Agonists

Published online by Cambridge University Press:  18 September 2015

S. Gauthier ,
R. Leblanc ,
R. Quirion ,
G. Carlsson ,
M. Beaulieu ,
R. Bouchard ,
D. Dastoor ,
F. Ervin ,
L. Gauthier  and
M. Gauvin
...Show all authors
S. Gauthier*
Affiliation:
Montreal Neurological Hospital and Institute
R. Leblanc
Affiliation:
Montreal Neurological Hospital and Institute
R. Quirion
Affiliation:
Douglas Hospital Research Centre
G. Carlsson
Affiliation:
Intermedics Infusaid Inc.
M. Beaulieu
Affiliation:
Sandoz Canada Research Department
R. Bouchard
Affiliation:
Hospital de l'Enfant Jesus
D. Dastoor
Affiliation:
Douglas Hospital Research Centre
F. Ervin
Affiliation:
Allen Memorial Institute
L. Gauthier
Affiliation:
School of Physical and Occupational Therapy, McGill University
M. Gauvin
Affiliation:
Montreal Neurological Hospital and Institute
J. Henry
Affiliation:
Allen Memorial Institute
R. Palmour
Affiliation:
Allen Memorial Institute
Y. Robitaille
Affiliation:
Montreal Neurological Hospital and Institute
*
Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, Canada H3A 2B4
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Abstract:

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Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

Type
Clinical and Therapeutic Issues
Information
Canadian Journal of Neurological Sciences , Volume 13 , Issue S4 , November 1986 , pp. 394 - 402
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

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