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Magnesium pemoline, a mild stimulant of the central nervous system, enhances the acquisition and retention of a conditioned avoidance response in rats. Methamphetamine and methylphenidate do not have this effect.
The effect of magnesium pemoline on the synthesis of brain RNA in vivo was studied. No significant effect either on the concentration of RNA or on the uptake of H(3)-uridine into RNA was detected.
Rats administered 20 milligrams of magnesium pemoline per kilo gram of body weight learned to avoid shock in a jump-out apparatus in fewer trials than did controls. However, the results suggested that the principal effect of the drug was to facilitate the avoidance behavior of those animals that tended to "freeze" in response to electric grid shock. No differences in retention were observed between experimental and control animals that had achieved equal levels of learnine.
Pemoline-C(14) dissolved in dimethyl sulfoxide and injected intraperitoneally into rats was found in larger amounts in the brain than was a similar dose given in 0.3 percent tragacanth suspension. This appeared to be related to a partial breakdown of the blood-brain barrier in vivo by the dimethyl sulfoxide.
Diagnosis of attention deficit disorder in a 35-year-old man and treatment with pemoline substantially improved his response to alcoholism treatment and aftercare. The authors conclude that treatment of attention deficit disorder may aid in rehabilitation of alcoholic patients.
A solid-phase extraction and reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for the rapid determination of 13 diuretics (belonging to five different pharmacological groups), probenecid, caffeine and pemoline in urine. Two ml urine sample was first adsorbed on a XAD-2 column, then eluted with ether-ethyl acetate (1:1). The eluate was evaporated to dryness and reconstituted in methanol. The methanolic solution was injected into a HP LiChrosorb RP-18 column, using phosphate buffer (pH 3) and acetonitrile as the mobile phase and monitored at 216 nm, 230 nm, and 275 nm on a diode array ultraviolet detector. The extraction recoveries of 16 drugs were above 75%. The limits of detection ranged from 0.3-3.0 micrograms/ml of urine. All drugs were separately administered to healthy volunteers, positive urine samples were collected, and urinary excretion-time curves of some drugs were reported.
The disposition kinetics of pemoline after iv and oral administration of 2.4 mg/kg of the drug were studied. The elimination half-life was 39.4 hr. The mean volume of distribution was 1.5 liters/kg indicating extensive tissue distribution and sequestration for an amphoteric drug. Plasma protein binding determined by in vitro equilibrium dialysis was concentration dependent. The mean binding capacity was found to be 0.80 mu-mol/g, an apparent dissociation constant of 3.73 X 10(-5) molar, and a total plasma protein concentration of 64.7 g/liter. The mean systemic availability by oral administration was 84.8% with an absorption half-time of 4.9 hr. The time course relationship showed that locomotor activity was directly related to the doses studied.
Acute or repeated treatment with Mg-Pemoline (Mg-Pg) did not modify the endogenous level of brain catecholamines (CA) of rats. However, a single dose (30 mg/kg) produced a significant decrease of brain CA turnover, measured either by the rate of conversion of 14C-tyrosine to CA or by the rate of disappearance of CA after alpha-MT. Mg-Pe (0.01-0.1 mM) did not modify the basal outflow nor the release of 3H-DA elicited by high K+ in slices of corpus striatum. At the same concentrations, Mg-Pe inhibited uptake of DA (competitively) or NA (uncompetitively) in synaptosomes from corpus striatum and hypothalamus, respectively. Turning-behavior in mice lesioned in corpus striatum with 6-OH-DA, indicated that this drug acts like amphetamine as an indirect DA agonist. These results suggest that central stimulant effects of Mg-Pe may be the consequence of CA-uptake inhibition and this effect may also account for the decrease of brain CA turnover.
We present a case of pemoline-induced autoimmune hepatitis in a 46-yr-old woman who received the drug for management of her multiple sclerosis. The autoimmune nature of the hepatitis is based on elevation of her anti-nuclear antibodies, anti-thyroid antibodies, IgA, and IgM globulins. These features of autoimmunity disappeared with normalization of her liver-associated enzymes and have remained negative for at least 6 months after completion of prednisone therapy.
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