3',5' Cyclic Adenosine Monophosphate in Depression and Mania

Pharmacological properties of centrally administered ouabain and their modification by other drugs

“…In contrast, pretreatment with nialamide, 10 or 20 mg/kg intraperitoneally, 2 h before intracerebroventricular ouabain, 0 3 ,fg, failed to reduce or retard the development of central nervous depressant effects, although the rate of recovery from the ouabain effect was significantly enhanced by the MAO inhibitor, (P= <0 05). Abdulla & Hamadah (1970) have shown that the successful treatment of clinical depression with antidepressant drugs was accompanied by an increase in urinary concentrations of cyclic 3',5'-AMP(cAMP); since intracerebroventricular ouabain produces, in mice, central nervous depressant effects which are similar to those of reserpine, and these same workers claimed reserpine ptosis can be reversed by dibutyryl cyclic 3',5'-AMP(dbcAMP), an attempt was made to antagonize the de-pressant effects of intracerebroventricular ouabain with concomitantly administered dbcAMP; this agent was used because it can cross cell membranes more readily than its analogue cAMP (Butcher & Sutherland, 1962, and its rate of hydrolysis by phosphodiesterase is very much slower than that of cAMP (Moore, Iorio & McManus, 1968). Groups of five mice were given, by intracerebroventricular injection, ouabain alone, 03 ,ug, dbcAMP alone, 25 ,ug, or a mixture of 'both in the same injection.…”

“…The experiments with dbcAMP and caffeine were prompted by the experiments of Abdulla & Hamadah (1970), in which they claimed that the successful treatment of clinical depression by thymoleptics was associated with an increased urinary excretion of cAMP. Field, Plotkin & Silen (1968) have demonstrated an antagonism between the cardiac glycosides and cAMP on ion permeability.…”

Biochemical assessment of antidepressive drugs.

“…It is formed from adenosinetriphosphate by the action of the enzyme adenylcyclase and is degraded by the enzyme c-AMP phosphodiesterase; both of these occur in the brain. Although the role of c-AMP in the pathogenesis of affective disorders remains inconclusive (Abdulla & Hamadah, 1970;Eccleston, Loose, Puller and Sugden, 1970), it has been suggested that NA sensitive adenylcyclase in the brain may be involved in the mechanism of action of antidepressive drugs (Vetulani & Sulser, 1975). TCA antidepressive drugs inhibit phosphodiesterase (Janice, Korczak & Herman, 1971) and may increase the accumulation of c-AMP in brain (Huang & Daly, 1972).…”

“…In addition, c-AMP is also related to physical exercise (Eccleston et al, 1970) and anxiety states (Moyes & Moyes, 1977). Hence, the methodologies used to measure c-AMP in urine (Abdulla & Hamadah, 1970) and in CSF (Robinson, Coppen, Whybrow & Prange, 1970) are unlikely to be helpful in the assessment of drug interactions in man.…”

Pharmacological properties of centrally‐administered agents which interfere with neurotransmitter function: a comparison with the central depressant effects of ouabain

“…A decrease in locomotor activity was apparent within Earlier experiments showed that icv dbc AMP can antagonize the hypothermia and behavioural depressant effects produced by icv ouabain. Since icv ouabain produces behavioural effects similar to those of peripherally-administered reserpine, and because Abdulla & Hamadah (1970) have reported that reserpine ptosis can be reversed by dbc AMP, the interaction between icv dbc AMP and peripherally-administered reserpine was examined.…”