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Marks V, Morris BA, Teale JD. 
“Pharmacology”. 
Brit Med Bull. 1974;30(1):80-86.
Abstract
The Authors consider the application of radioimmunoassay to pharmacology. Radioimmunoassay (RIA) involves the production of antibodies to the drugs under test. The drug is rendered immunogenic by coupling to a large antigenic molecule such as bovine serum albumin. Measurement of a drug by saturation analysis depends upon its ability to compete with a labeled compound for a binding reagent; the nature of the label influencing the sensitivity of the assay. Labeling techniques include radioisotopes, steric inhibition by enzymes and attachment of a free radical to the hapten. RIA had been applied to the following drug groups: a) Cardiac glycosides: RIA uses antibodies raised in rabbits to either digoxin or digitoxin although cross reactivity is known to occur. (3H) digoxin and the 25I-labeled tyrosine derivative of digoxin have recently been used as tracers. b) Morphine and opiate alkaloids: Most RIA methods depend on antisera raised to morphine coupled to carrier protein at the 3-OH position. Labels used, include 7,8-(3H)dibydromorphine, (14C)- morphine and 25I-labeled conjugates-of 3 - carboxymethylmorphine and an assay sensitive to 1 ng/ml has been developed. c) Prostaglandins: Antisera can distinguish between the various prostaglandin classes although class separation is required for accurate measurement. RIA can be useful in the diagnosis of medumcgry carcinoma of the thyroid but the main -application is in the monitoring of prostaglandin therapy. d) Lysergic acid derivatives: Antibodies to lysergic acid (LSD, lysergide) can be produced by immunising against a conjugate of D-lysergic acid with poly-L-lysine; the sensitivity of the assay being I pmol D-lysergic acid with antiserum dilution of 1:30,000. Antibodies produced against LSD-human serum albumin give a more sensitive assay of 50 fmol LSD. e) Tetrahydrocannabinol (cannabis): Albumin and tyrosine con-jugates of tetrabydrocannabinol (THC) are produced. The structure of THC permits formationofauccinylandchlorocarbonate derivatives prior to albumin linkage. f) Anticonvulsants; barbiturates and phenytoin: Antisera are raised to an immunogen prepared by converting 5-allyl-5-(1-carboxy- lisopropyl)barbituricacid'op-nitrophenol derivative before conjuga-tion with bovine immunoglobulin. Barbitone, phenobarbitone and pentobarbitone react well and 500 ng/ml drug can be detected. Phenytoin RIA using (4C)phenytoin is sensitive to 300 ng/ml. g) Miscellaneous drugs and vitamins: RIA can be used to detect amphetamines, phenothiazines tubocurarine, vitamin D and 25 -hydroxycalciferol.
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