Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats.

Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task.

Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting.

Rationale: Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present.

Objective: The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models.

HIF prolyl hydroxylase inhibition augments dopamine release in the rat brain in vivo.

The transcription factor hypoxia-inducible factor (HIF) is essential for the activation of several genes that promote the survival of cells exposed to oxidative stress. Expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme in the dopamine (DA) synthesis, is one of the genes that are positively regulated by HIF. Accordingly, HIF induction results in elevated DA release in various cell lines in vitro.

In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release.

A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(-1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in Viscoleo/castor oil 2:1 (v/v) administered s.c.

Characteristics of drug substances in oily solutions. Drug release rate, partitioning and solubility.

In vitro rate of drug release from oil solutions was investigated in a rotating dialysis cell. A log linear correlation was established between the rate constant (k(obs)) for attainment of equilibrium and apparent partition coefficient (P(app)) between oil vehicle and release media using various weak acids and bases and non-electrolytes. Collander like linear free energy relationships were observed allowing various oil-aqueous buffer partition coefficients to be calculated from known octanol-aqueous buffer partition coefficients.