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Biomedical subjects
Publications and source records attributed to I Heath.
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The comparative behavioral and neurochemical activities of the muscarinic cholinergic antagonists scopolamine, trihexyphenidyl and pirenzepine, and the nicotinic cholinergic antagonist mecamylamine were evaluated in rats. The three muscarinic antagonists, but not the nicotinic antagonist, impaired memory performance in a spatial alternation task. The minimal effective doses required to disrupt behavior were 0.03, 1.0 and 10 mg/kg for scopolamine, trihexyphenidyl and pirenzepine, respectively. Scopolamine and trihexyphenidyl inhibited ex vivo binding of [3H] pirenzepine to M1 receptors in cerebral cortex, indicating ready penetration into the brain. In contrast, pirenzepine penetrated into the brain at relatively high doses, suggesting poor penetration into the brain. Scopolamine and trihexyphenidyl, but not pirenzepine, inhibited [3H]quinuclidinyl benzilate binding to brain stem M2 receptors ex vivo after subcutaneous administration. In addition, scopolamine and trihexyphenidyl, but not pirenzepine, decreased acetylcholine (ACh) levels in striatum and hippocampus, presumably by increasing ACh release by blocking ACh feedback inhibition at M2 receptors. Scopolamine and trihexyphenidyl also produced modest decreases in levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in striatum, most likely due to blockade of M1 heteroreceptors on dopamine nerve terminals. The present results are consistent with the interpretation that muscarinic antagonists impair memory performance in rats, at least in part, by blocking M1 muscarinic receptors. The present results do not support a role for blockade of M2 receptors. Further research is needed to determine the extent to which blockade of other (M3, M4, M5) muscarinic receptor subtypes contributes to the memory-impairing effects of muscarinic cholinergic antagonists.
Vasoconstriction occurs in the skin capillary blood flow of the healthy subject when posture changes from supine to standing. Using frequency analysis of the optical photoplethysmograph signal, a statistically significant difference (P less than 0.01) may be demonstrated between supine and standing positions in the lower frequency band (0.01-0.5 Hz) in the foot of normal subjects. This allowed us to develop a simple index: sympathetic power band change (SPBC). Patients with diabetes mellitus often suffer from degeneration in the sympathetic nervous system. This impairs the normal vasoconstrictor response to standing. We have applied the SPBC 'blind' to a group of diabetic patients. Such patients may be divided into three groups according to their SPBC indices: normals with SPBC greater than 2.6 (group A), intermediates with 2.6 greater than or equal to SPBC greater than or equal to 0.26 (group B) and poor with SPBC less than 0.26 (group C). All patients with retinopathy were in group C and five out of the six patients with electrophysiologically confirmed peripheral neuropathy were in group C. Frequency analysis of the photoplethysmograph signal has produced an index of sympathetic tone change when subjects move from supine to standing position. The application of this index to patients with diabetes mellitus shows some patients to have sympathetic vascular tone failure.
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