Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Transmitter-replacement therapy in Alzheimer's disease using intracerebroventricular infusions of receptor agonists. 287 12

Bethanechol chloride, a muscarinic agonist, was administered intrathecally to a sample of AD patients in double-blind crossover and open escalating-dose trials. There was a modest amelioration of disturbed behavior at a moderately high dose level, but no improvement in memory or cognition was seen at any dose. At the highest dose, cognition deteriorated. These findings, in conjunction with the results of the multicenter trial described by Harbaugh, suggest that the clinical efficacy of bethanechol in AD is limited. The disappointing results of trials with varied cholinomimetic therapies suggest that more than one biochemical abnormality is responsible for the AD dementia. The neuropeptide, somatostatin, is also reduced in AD, and the level of reduction is correlated with the degree of dementia. Manipulation of this transmitter, alone or in conjunction with acetylcholine, would appear to be a next logical step in the development of an effective neurotransmitter replacement therapy for AD. Implanted drug pumps will be needed for such clinical trials. The naturally occurring somatostatin-14 is not suitable because of its short half life. Sandostatin, an analog, is chemically stable and not metabolized by brain tissue. It does not cross the blood-brain barrier so that intrathecal administration is necessary. Pharmacological research in AD is complicated by a variety of psychometric problems including the criterion-related and construct validity of the outcome measures. Patients differ in their tolerance of various therapeutic agents and in the extent of the neurochemical pathology. It is critically important, therefore, to evaluate individual, as well as group, responses to treatment. The telephone log method may provide a useful way of generating enough observations for single subject analyses without overburdening the patient with repeated testing.
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PMID:New intrathecal drugs in Alzheimer's disease and psychometric testing. 289 28