GPAT Notes - 7

POLARITY ORDER:

cyclohexane

n-hexane

n-decane

i-octane

octane

butyl ether

carbon tetrachloride

triethyl amine

i-propyl ether

toulene

xylene

t-butyl methyl ether

benzene

benzyl ether

dichloromethane

methylene chloride

chloroform

dichloro ethane

ethylene dichloride

butanol

i-butyl alcohol

tetrahydrofuran

ethylacetate

propanol

methylacetate

cyclohexanone

methyl ethyl ketone

nitrobenzene

benzonitrile

1,4-dioxane

ethanol

nitroethane

pyridine

acetone

benzyl alcohol

methoxy ethanol

acetic acid

acetonitrile

N,N-dimethylformamide

dimethyl sulfoxide

methanol

formamide

water

Blood brain Barrier

Our brain is protected by BBB to prevent the entry of noxious substances and is permeable only to the highly lipophilic drugs..but the question which arises here is how come glucose and other nutrients which are polar find their way into the brain..

Glucose has its transporters (GLUT or SLC2A family) which are divided into 3 classes-GLUT1 is expressed in BBB and GLUT4 in the neurons which help in the uptake of glucose

Coming to the other nutrients-astrocytes are the helping cells which help in providing metabolites like lactate and aminoacids which are modified into neurotransmitters..

Vitamins which form the major class of cofactors are transported via the sodium dependent multivitamin transporters..out of which sodium dependent vitamin C transporter(SVCT2) is very important physiologically..as Vitamin C is proposed as a neuromodulator of glutamatergic, dopaminergic, cholinergic, and GABAergic transmission and related behaviors.

Coming to the CNS drugs..most of them are prepared such that there is a predominant nonpolar moeity in it which helps in its transport,in diseased states like meningitis or other inflammatory conditions the BBB is weakened and hence polar drugs can find their way,or else mannitol or other osmotic agents can be used to disrupt the BBB prior to the administration of drug,so that it can enter brain ; other targetted delivery system include dihydropyridine-drug complex which facilitates the drug entry.

The current delivery system which is under experiments is delivery of drugs to brain by adding a component of Vit C,so that it is transported via the SVCT2 transporter which showed promising results in animal trials for delivering drugs treating alzheimer's disease...if it is succesful in human trials then is a new drug delivery system..:)