Central vs. Peripheral Stimulant Effects

[hussness]

I've heard about central vs. periferal effects of stimulants and assume that refers to CNS vs. PNS. What is it that would favor a molecule weighing heavily on the PNS vs CNS side? BBB impermeability? How about something that was more CNS vs. PNS?

 

[fastandbulbous]

^ Pretty much. That's one of the main reasons why ephedrine doesn't have the same abuse potential as methamphetamine, even though they're only different in structure by a hydroxy group.

Best guide to BBB permeability of a drug is its 1-octanol/water partition coefficient

 

[hussness]

This is probably a stupid question, but can it go the other way? I mean some drug that was not delivered intercranially but had a disproporionately large CNS verses PNS effects?

 

[BilZ0r]

^ Probably not really. Extremely fat soluble chemicals still have to distribute around the body. And brain concentrations can't increase above plasma concentrations.

What is likely is that low noradrenaline transporter binding will make it feel like it has less peripheral stimulation.

 

[ebola?]

>>^ Pretty much. That's one of the main reasons why ephedrine doesn't have the same abuse potential as methamphetamine, even though they're only different in structure by a hydroxy group.>>

Hmmm...does this indicate that intercranially administered ephedrine would be great fun?

ebola

 

[Smyth]

I understand the principle of lipophilicity.

^Howcome then the tricyclic antidepressants are nothing like amphetamine then even though they are N(E/A)T inhibitors?

Norepinephrine activity is not solely responsible for stimulation then although as a general rule of thumb it does seem as though it would br indicated.

I doubt it can be solely down to antihistamine activity since someone who is on speed will hardly be put to sleep by something like this:

But take a dose of Amitriptyline and it will lay a nigga out cold despite being cardiotoxic.

 

[fastandbulbous]

Howcome then the tricyclic antidepressants are nothing like amphetamine then even though they are N(E/A)T inhibitors

Amphetamines aren't just reuptake inhibitors, they also cause release of noradrenaline & dopamine as well as acting as reuptake inhibitors for saud monoamines (add 5HT to the above if talking about methamphetamine)

 

[5-HT2]

^^^It's not just that, because cocaine is merely a reuptake inhibitor but it still gets you high. Pharmacodynamics and pharmacokinetics also play a very important role. In order to get you high, a reuptake blocker must get into your brain and onto your transporters quickly, otherwise the gradient of neurotransmitter increase is too shallow for your brain to sense (i.e. there is enough time for compensatory processes to kick in).

 

[Smyth]

I am still one of the few minority of people who is able to rush of as little as 25 mg of ephedrine or 60 mg pseudo. The trick is to take the tablet first thing in the morning with a couple of cups of a caffeinated beverage such as coffee, tea, coke etc. The effects are rather modest but strong enough to be noticeable. Also, like antidepressants I think that it might be a chronic thing that only happens after a few weaks of sustained use. I also smoke cigarettes and drink alcohol and these have defintate effects of the central nervous system also.