Methods and findings in experimental and clinical pharmacology
March 1, 2000
L B Hough, A A Bagal, S D Glick
7 citations
After a 20 mg/kg intravenous infusion in rats, ibogaine levels in plasma declined rapidly in a two-phase pattern, with an initial half-life of 7.3 minutes and a terminal half-life of 3.3 hours. Drug clearance was 5.9 L/h. Three hours after infusion, ibogaine concentrations in brain, liver, and kidney were 143–170 ng/g, but in adipose tissue the concentration was much higher at 3,328 ng/g. This sequestration in fat likely causes the drug to persist in the body longer than the terminal half-life suggests. The initial rapid disappearance from plasma may result from metabolic demethylation and redistribution to tissues.
Methods and findings in experimental and clinical pharmacology
May 1, 2007
T Enomoto, Y Noda, T Nabeshima
The noncompetitive NMDA receptor antagonist phencyclidine (PCP) produces a schizophrenia-like psychosis in humans, including positive symptoms, negative symptoms, and cognitive dysfunction. PCP-treated animals show hyperlocomotion, social behavioral deficits, enhanced immobility in forced swimming, sensorimotor gating deficits, and cognitive dysfunctions, some of which persist after withdrawal from repeated treatment. Repeated PCP treatment also induces neurochemical and neuroanatomical changes. Genetic animal models based on the glutamate hypothesis of schizophrenia, such as NMDA receptor subunit knockdown or knockout mice, also exhibit schizophrenia-like behaviors. These PCP and genetic models are useful for evaluating novel therapeutic candidates and studying pathological mechanisms of schizophrenia.
Methods and findings in experimental and clinical pharmacology
November 1, 2001
M Gupta, S Balakrishnan, P Pandhi
The nitric oxide precursor L-arginine reduced amphetamine-induced repetitive behaviors and haloperidol-induced movement stiffness in rats, while enhancing conditioned avoidance. The nitric oxide synthase inhibitor L-NOARG had opposite effects: it increased repetitive behaviors and stiffness but reduced conditioned avoidance. No significant difference was observed between acute and five-day chronic administration of either compound. The authors conclude that nitric oxide has contradictory effects across different psychosis models, and L-arginine may have antipsychotic potential without causing extrapyramidal side effects.