Neurotransmitter replacement therapy in Alzheimer's disease.
The relative success of symptomatic attenuation of motor dysfunction in Parkinson's disease with dopaminomimetics has spurred interest in neurotransmitter replacement therapy for treating Alzheimer's disease. While cholinergic dysfunction has been linked to various clinical parameters in Alzheimer's disease, cholinergic replacement, including precursor therapy, administration of direct-acting agonists and inhibition of enzymatic degradation has had only very modest success. The inhibition of enzymatic degradation has perhaps shown the most interesting results to date. However, conclusions with respect to efficacy continue to be controversial. Discussion continues about whether or not single transmitter replacement for Alzheimer's disease is a viable treatment approach. Deficiencies in central noradrenergic, serotonergic, GABAergic and perhaps dopaminergic neural transmission may also play a critical role in some of the clinical manifestations of Alzheimer's disease. In addition, certain neuropeptides, in particular somatostatin, may be important in this context. Several series of clinical trials are currently attempting to address these issues. Given the complexities of the pathophysiology of Alzheimer's disease, symptomatic relief may require multiple transmitter replacement and necessitate more definitive intercessions at the molecular biological level.
Mohr
E
E
Institute of Mental Health Research, University of Ottawa, Ontario, Canada.
Mendis
T
T
Rusk
I N
IN
Grimes
J D
JD
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D012701:Serotonin / Q000494:pharmacology / Q000627:therapeutic use*; D013004:Somatostatin / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use*
D015259:Dopamine Agents; D012701:Serotonin; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid