Quetiapine Fumarate 111974-72-2

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Molecular Weight: 883.09 Quetiapine Fumarate is an atypical antipsychotic used in the treatment of schizophrenia, bipolar I mania, bipolar II depression, bipolar I depression.

Quetiapine shows affinity for various neurotransmitter receptors
including serotonin, dopamine, histamine, and adrenergic receptors and
has binding characteristics at the dopamine-2 receptor similar to those
of clozapine.

Quetiapine has a preclinical profile suggestive of antipsychotic
activity with a reduced tendency to cause extrapyramidal symptoms (EPS)
and sustained prolactin elevation. Guetiapine alters neurotensin
neurotransmission and c-fos expression in limbic but not motor brain
regions. Quetiapine also demonstrates clozapine-like activity in a range
of behavioral and biochemical tests and may possess neuroprotective
properties. Quetiapine dose-dependently prevents
schizophrenia and depression in hippocampal cell proliferation and BDNF
expression caused by chronic restraint stress (CRS) in rats.


Guetiapine
(5 mg/kg) combined with Venlafaxine (2.5 mg/kg) increases hippocampal
cell proliferation and prevents BDNF decrease in stressed rats, whereas
each of the drugs exerts mild or no effects. Guetiapine
produces selective effects on cortical and limbic regions of the brain
and in particular on dopaminergic neurotransmission in these regions.
Guetiapine produces lower levels of putamenal DA D2r occupancy than
those reported for typical APDs.


Quetiapine also produces preferential
occupancy of temporal cortical DA D2r, 46.9%, but does not spare
occupancy of substantia nigra DA D2r. Guetiapine
attenuates the decrease in levels of brain-derived neurotrophic factor
(BDNF) in the hippocampi of rats subjected to chronic-restraint stress.
Guetiapine (10 mg/kg) reverses the stress-induced suppression of
hippocampal neurogenesis, evidenced in the numbers of BrdU-labeled and
pCREB-positive cells that are comparable to those in non-stressed rats
but higher than those in the vehicle-treated rats.





Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

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