Abstract
The biological function, metabolism and excretion of cyclic AMP are reviewed. The effects of drugs on cyclic AMP metabolism are considered and the methods that have been used to assay cyclic AMP are summarised. The selected binding protein assay was modified slightly so that incubation could be carried out at room temperature. 70 drugs of wide ranging pharmacological action were tested as potential inhibitors of phosphodiesterase and the relevance of this inhibition to the situation in vivo is discussed. Cyclic AMP was stable in vitro in urine samples stored at room temperature, 4°C and -20°C for at least 2 days, 1 month and 3 months respectively. A phenyl mercuric nitrate and sodium fluoride tablet preserved cyclic AMP levels at room temperature for at least 6 weeks. Cyclic AMP was also stable in a bladder stored at 4°C for up to 3 days. Urine flow rate did not affect cyclic AMP excretion. The urinary cyclic AMP to creatinine ratio was found to have a higher mean value in women than in men (ie 4.3 as opposed to 2.9nmols/mg). The variation of the ratio was very similar for both sexes (ie coefficients of variation of 25% and 27% for men and women respectively). Two subjects were used as a screen to determine which factors influenced cyclic AMP excretion. In both subjects 24 hourly cyclic AMP excretion (coefficients of variation of 7% and 14%) and the cyclic AMP to creatinine ratios (coefficients of variation of 15% and 18%) were reasonably constant. A slight diurnal variation was observed for both subjects, Urinary pH, exercise, alcohol, vitamin C and therapeutic doses of amphetamine, amylobarbitone, imipramine and trifluoperazine had no significant effects on cyclic AMP excretion. The variation in creatinine excretion is considered and disease states that affect both creatinine and cyclic AMP excretion are discussed. Dying and the associated physical and biochemical changes are described. Poisoning by drugs and the use of potential biochemical markers of drug overdosage are discussed. Post mortem urines from natural deaths could not be distinguished from drug overdose victims in terms of the cyclic AMP to creatinine ratio. In both cases, however, there was considerably greater scatter than in urines obtained from living persons. Post mortem cyclic AMP levels were not effective markers of drug overdosage. However,the cyclic AMP excretion data may be of use in a clinical context and possible applications are discussed.