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.
1 Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol sulphate (MOPEG-SO(4)) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG-SO(4)/NA ratio was 0.28. Thereafter the MOPEG-SO(4) concentration declined and the NA concentration decreased further to 28% of control.2 Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG-SO(4).3 While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG-SO(4) concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG-SO(4).4 NA and MOPEG-SO(4) 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-SO(4) remained at approximately 70% of controls during the entire period.5 The probenecid-induced accumulation rate of MOPEG-SO(4) 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.6 These experiments indicate that MOPEG-SO(4) 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.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004558:Electric Stimulation; D006018:Glycols / Q000378:metabolism*; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D013997:Time Factors
D006018:Glycols; D008734:Methoxyhydroxyphenylglycol; D012110:Reserpine; D011339:Probenecid; D009638:Norepinephrine