Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone.

Catalepsy and changes in striatal and limbic dopamine metabolism were investigated in mice after oral administration of aripiprazole, haloperidol, and risperidone. Catalepsy duration decreased with chronic (21 day) aripiprazole compared with acute (single dose) treatment across a wide dose range, whereas catalepsy duration persisted with chronic haloperidol treatment. At the time of maximal catalepsy, acute aripiprazole did not alter neostriatal dopamine metabolite/dopamine ratios or homovanillic acid (HVA) levels, and produced small increases in dihydroxyphenylacetic acid (DOPAC).

Alteration of methamphetamine-induced striatal dopamine release in mint-1 knockout mice.

Mint-1, which is also called as X11 or mammalian Lin10, protein has been implicated in the synaptic vesicle exocytosis and the targeting and localization of synaptic membrane proteins. Here, we established mint-1 gene knockout (mint-1 KO) mice and investigated vesicular and transporter-mediated dopamine (DA) release evoked by high K(+) and methamphetamine (METH), respectively. Compared with wild-type control, high K(+)-evoked striatal DA release was attenuated, but not significantly, in the KO mice as measured by microdialysis method.

Intracerebral adenosine infusion improves neurological outcome after transient focal ischemia in rats.

Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan In order to elucidate the role of adenosine in brain ischemia, the possible protective effects of adenosine on ischemic brain injury were investigated in a rat model of brain ischemia both in vitro and in vivo.

Stimulation of the regrowth of MPP+-damaged dopaminergic fibers by the treatment of mesencephalic cultures with basigin.

Basigin (Bsg) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily and widely expressed in the central nervous system. To elucidate functional role of Bsg in the central nervous system, the effects of its glutathione-S-transferase (GST) fusion protein on the number and neurite outgrowth of cultured rat mesencephalic dopaminergic neurons were measured. The fusion protein was not able to promote the survival and neurite outgrowth of tyrosine hydroxylase (TH)-positive neurons under serum-free condition.

Orally active, nonpeptide vasopressin V2 receptor antagonists: a novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds.

This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity.

Structure-activity relationships of non-peptide vasopressin V1a antagonists: 1-(1-multi-substituted benzoyl 4-piperidyl)-3,4-dihydro-2(1H)-quinolinones.

During our systematic studies on the arginine vasopressin receptor V1a-antagonistic activity of 1-(1-benzoyl substituted 4-piperidyl)-3,4-dihydro-2(1H)-quinolinones, we found a general substituent effect on the benzene ring. Hydrogen-bonding ability at the ortho position was especially important for enhancement of the affinity of multi-substituted analogs. Details of the syntheses and structure-activity relationships for this series are presented.

Novel thiazole derivatives as inhibitors of superoxide production by human neutrophils: synthesis and structure-activity relationships.

Neutrophils have an important role in the self-defense systems of organisms through the production of superoxide. On the other hand, it has been proposed that abnormal amounts of superoxide produced by neutrophils are a serious factor in tissue injury. A series of novel thiazole derivatives was prepared and evaluated inhibitory effect on superoxide production by human neutrophils in vitro.

Orally active, nonpeptide vasopressin V1 antagonists. A novel series of 1-(1-substituted 4-piperidyl)-3,4-dihdyro-2(1H)-quinolinone.

A series of compounds has been synthesized and demonstrated to be antagonists of V1 receptors both in vitro and in vivo. These compounds are structurally related to the 1-(4-piperidyl)-2(1H)-quinolinones, including OPC-21268, an orally bioavailable AVP V1 antagonist with high V1 specificity. It has been found that the introduction of an acetamide group on the terminal alkoxy chain of 41-44 leads to an increase in oral activity.