Mental dysfunction and the blockade of muscarinic receptors in the brains of the normal elderly

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 9; no. 5-6; p. 651
• Main Authors: Richardson, J S, Miller, P S, Lemay, J S, Jyu, C A, Neil, S G, Kilduff, C J, Keegan, D L
• Format: Journal Article
• Language: English
• Published: England 1985
• Subjects: Aged; Female; Humans; Male; Memory, Short-Term - drug effects; Mental Disorders - chemically induced; Mental Disorders - physiopathology; Parasympatholytics - adverse effects; Scopolamine - pharmacology
• ISSN: 0278-5846
• DOI: 10.1016/0278-5846(85)90034-X

Cholinergic neurons innervate many areas of the brain and the disruption of acetylcholine neurotransmission at the muscarinic receptors in these areas produces dysfunction in a wide variety of mental, emotional and physiological activities. A side effect of many psychoactive drugs is the blockade of muscarinic receptors and this can result in a marked reduction of acetylcholine neural function particularly in elderly patients receiving 2 or more such drugs, and mimic the mental impairments seen in Alzheimer's Disease. A battery of mental status and short term memory tests was given the day before and 45 minutes after the administration of 0.005 mg/kg scopolamine or saline as presurgery medication to 30 normal patients over 60 years of age scheduled for lower body surgery. Total antimuscarinic activity was determined using a competitive binding assay in a 10 ml sample of blood taken from all patients after the pretest and again at the time of surgery, and in a 2 ml sample of cerebral spinal fluid taken from patients receiving spinal anesthesia immediately prior to administering the anaesthetic. The very low dose of scopolamine given to these patients produced antimuscarinic activity equivalent to 100 pmoles atropine in serum and 74 pmoles atropine in CSF. This resulted in a significant impairment of short term memory but had no significant effect on global scores on the Mini Mental State nor on the Delirium Check List.