SHORT AND LONG-TERM EFFECTS OF RESERPINE ON THE CONCENTRATION OF 1-(4-HYDROXY-3-METHOXYPHENYL)-ETHANE-1,2-DIOL (MOPEG-SO4) IN THE BRAIN OF THE RAT

Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1‐(4‐hydroxy‐3‐methoxyphenyl)‐etnane‐1,2‐diol sulphate (MOPEG‐S04) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG‐S04/NA ratio was 0.28. Thereafter the MOPEG‐SO4 concentration declined and the NA concentration decreased further to 28% of control. Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG‐SO4. While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG‐SO4 concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG‐SO4. NA and MOPEG‐SO4 concentrations were examined during 5 days after a single dose of reserpine (1.25 mg/kg i.p.). While the concentration of NA started to return towards normal after 24 h, that of MOPEG‐SO4 remained at approximately 70% of controls during the entire period. The probenecid‐induced accumulation rate of MOPEG‐SO4 was significantly lower 3 and 4 days after reserpine and returned to the control value on the fifth day. At this time the concentration of NA had reached 50% of the control value. These experiments indicate that MOPEG‐SO4 is not the major metabolite of NA during the initial phase of reserpine‐induced NA release. Reserpine acts on the storage pool while amphetamine (like electrical stimulation) acts on the functional pool. During the first phase of post‐drug recovery, there is a clear decrease in NA output which appears to be regulated by the concentration of NA in the storage pool. 1979 British Pharmacological Society