Clozapine and the mitogen-activated protein kinase signal transduction pathway: Implications for antipsychotic actions was written by Browning, Jeff L.;Patel, Tushar;Brandt, Paul C.;Young, Keith A.;Holcomb, Leigh A.;Hicks, Paul B.. And the article was included in Biological Psychiatry in 2005.COA of Formula: C11H13IN4O4 The following contents are mentioned in the article:
Mitogen-activated protein kinase (MAPK) signaling pathways respond to dopaminergic and serotonergic agents and mediate short- and long-term effects of intracellular signaling in neurons. Here we show that the antipsychotic agent, clozapine, selectively activates the MEK/ERK MAPK pathway, and inhibition of this pathway reverses clozapine’s actions in the conditioned avoidance response (CAR) paradigm, a rodent behavioral assay of antipsychotic activity. Phosphorylation patterns of MAPK pathway enzymes were determined by quant. immunoblot anal. and immunohistochem. of rat prefrontal cortex. Kinase inhibitors were used to assess the role of MAPK signaling pathways in mediating clozapine-induced suppression of CAR. Clozapine administration selectively increased phosphorylation of MEK1/2 but had no effect on p38 or JNK phosphorylation. Pretreatment with the 5-HT2A agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride blocked the clozapine-induced increase in MEK1/2 phosphorylation. Immunohistochem. revealed that clozapine treatment elevated the number of cells in the prefrontal cortex pos. for phosphoERK, the downstream substrate of MEK1/2. Prior administration of MEK1/2 inhibitors U0126 or Sl327, or ERK inhibitor 5-iodotubercidin, reversed suppression of CAR induced by clozapine, whereas administration of vehicle, JNK or p38 inhibitors (L-JNK-1 and SB203580, resp.) had no effect. Inhibition of kinases upstream to MEK1/2 (PI-3K, PKC, and CaMKII) by administration of LY294002, bisindolylmaleimide, or KN-62, resp., also reversed clozapine-induced suppression of CAR. These data support the hypothesis that the MEK/ERK signal transduction cascade participates in clozapine’s antipsychotic actions. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4COA of Formula: C11H13IN4O4).
(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. Tetrahydrofurans and furans are important oxygen-containing heterocycles that often exhibit interesting properties for biological applications or applications in the cosmetic industry. Tetrahydrofuran reaction with hydrogen sulfide: In the presence of a solid acid catalyst, tetrahydrofuran reacts with hydrogen sulfide to give tetrahydrothiophene.COA of Formula: C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem