The Methyl Group's Action

[Acyl]

That couldnt be the case, heroin still causes massive histamine releases..

I dont know about the drug having intrinsic activity, never heard this before... it seems like it would be lower than that of morphine to me? I read once that the hydroxyl groups from the aryl and the cyclohexane are at the edge of the receptors and are held there by water molecules forming hydrogen bonds. The acetyl groups would surely decrease the waters ability to keep em in place me thinks.

 

[fastandbulbous]

^ But the active molecule in the case of heroin is actually 6-acetylmorphine - the phenolic OH group is free to act in exacxtly the same way as it does in morphine

 

[Acyl]

That would make more sense

 

[IHateOpiophobes]

I thought the two branching oxygens and their dipole moments would increase the solubility/polarity, of the molecule.
Greater solubilty = equals BBB passage quicker and more efficiently.

You would also have more openings for hydrogen bonding which would further back up what I was saying. H-bonds increase polarity (or solubility in water, which just happens to make up approx 68-72 % of the human body; usually quite greatly.

So it boilds down (from boiling with to make the heroin) solubility via opening up possible hydrogen bonds. This also increases the gibbs free energy (ability to do work) and lowers enthalpy (release of energy, = HAPPY BONDS AND MOLECULES)

Adding those relatively inert groups who's only reactivity is with dissolving in water, won't affect how it hits the receptor. Just lowers the energy required for the morphine molecule to get their after first pass metabolism cleaves the two acetyl groups anyways. Think of those two groups as molecular rocket boosters, which fall off after they provide (or lower) the energy to get from point A to point B.

Not sure what they're called, but everyone has seen the........."Booster Rockets.......thats it, on a space shuttle or with a rocket launch.

just my 2 cents.

 

[MurphyClox]

I thought the two branching oxygens and their dipole moments would increase the solubility/polarity, of the molecule.
Greater solubilty = equals BBB passage quicker and more efficiently.[1]

You would also have more openings for hydrogen bonding which would further back up what I was saying.[2] H-bonds increase polarity [3] (or solubility in water, which just happens to make up approx 68-72 % of the human body; usually quite greatly.

So it boilds down (from boiling with to make the heroin) solubility via opening up possible hydrogen bonds. This also increases the gibbs free energy (ability to do work) and lowers enthalpy (release of energy, = HAPPY BONDS AND MOLECULES) [4]

Adding those relatively inert groups [5] who's only reactivity is with dissolving in water, won't affect how it hits the receptor.[6] Just lowers the energy required for the morphine molecule to get their after first pass metabolism cleaves the two acetyl groups anyways. Think of those two groups as molecular rocket boosters, which fall off after they provide (or lower) the energy to get from point A to point B.

Not sure what they're called, but everyone has seen the........."Booster Rockets.......thats it, on a space shuttle or with a rocket launch.

just my 2 cents.

My sincere apologies to the board administration for bumping this rather old thread but I just can't pass and let this bullshit happen...

[1] Dipole moments of esters?! WTF? Stop talking nonsense (as you are regularly doing in any advanced topic I saw). The natural solvent of living organism is fucking water. Therefore, increased solubility does NOT equal quicker BBB-passage. Reason: The BBB is a lipophilic (read: hydrophobic) barrier. Any increased solubility happens due to hydrophilic groups.
Extreme examples are charged molecules, which do not cross the BBB at all (unless there are specific transporters).

[2] Certainly not.

[3] This statement in particular is futile and just exhibits the gross lack of chemical knowledge. Hydrogen bonds do NOT increase polarity of a molecule, but they are rather formed preferentially by polar molecules (I'm simplifying here for brevity). The point is that in the above statement cause and effect were clearly confused.
And for the cases of intramolecular hydrogen bonds, the general tendency is that these decrease polarity, because they 'fix' protons in their position. The last mentioned effect may be quite small, I don't have numbers at hand.

[4] Please repeat your basics in physical chemistry. Happy bonds and molecules? I just can't believe this nonsense...

[5] First, the definition of "inert" is "not chemically reactive". You definitively used this term wrong.
Second, chemical reactivity is usually not a significant property of a pharmaceutical substance. I'd rather prefer that drugs do not react within my body (exceptions include prodrugs), for other reasons than metabolic degradation.

[6] Well, while this view is commonly accepted, I wouldn't be this sure. Weren't there some evidence that heroine has it's own pharmacological activity, i.e. does not act solely as prodrug?


I'm sorry if my post is considered as 'mindless flaming'; at least its absolutely not 'mindless' in this respect. In the light of the recently announced "Spring Cleaning" it really hurts my eyes to read such ... AH!... you get my point.

Peace! Murphy

 

[Hammilton]

^ No, you're right, this nonsense is that status quo for this particular user. You're certainly better than I am at criticising it though!

 

[LabRatNW]

Why wouldn't tertiary amines be more polar than secondary, it seems like they would follow the trend. more Inductive forces from the extra R group would push electron density to the Nitrogen. More separation of Charge. equals more polar.

The charge is spread out over more electron density, and more centers, meaning less polarity concentrated at the N center.

Secondary amines: Maybe the single unpaired electron is fluorine-like at that point. The electron configs of the F-radical and 2ndary-N are relatively alike... 3 filled/paired orbitals, one lone electron at a relatively electronegative center.