GABA analogs and the BBB

[snapper]

In SWIMS eternal quest for GHB analogs, SWIM got to thinking. GBL turns into GHB in vivo, but what about GABA analogs that cross the blood brain barrier and then lose the extra functional group to become GABA. GHB exerts its effect by turning into GABA in the brain. This line of thinking lead SWIM to pyrroline, which should metabolize to GABA in vivo and crossed the BBB. SWIM can find no commercial source for this molecule, but it should work similarly to GBL.
Here is an abstract which supports this :
Here is the link to PubMed :
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

J Neurochem. 1982 Apr;38(4):1063-7. Pyrrolines as prodrugs of gamma-aminobutyric acid analogues. Callery PS, Geelhaar LA, Nayar MS, Stogniew M, Rao KG.

delta 1-Pyrroline, 5-methyl-delta 1-pyrroline, and 5,5-dimethyl-delta 1-pyrroline have been identified as substances metabolized to gamma-aminobutyric acid (GABA), 4-aminopentanoic acid (methylGABA), and 4-amino-4-methylpentanoic acid (dimethylGABA), respectively. An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of delta 1-pyrroline to GABA and its lactam, 2-pyrrolidinone. Acetaldehyde, allopurinol, and cyanide inhibited the reaction. Incubation of deuterium-labeled delta 1-pyrroline with mouse brain homogenates produced deuterated GABA. Mouse liver 10,000 g supernatant and mouse brain homogenates converted 5-methyl-delta 1-pyrroline to methylGABA, and 5,5-dimethyl-delta 1-pyrroline to dimethylGABA. Four hours after intraperitoneal injection of 5-methyl-delta 1-pyrroline (200 mg/kg), methylGABA was detected in mouse brain (0.27 mumol/g). DimethylGABA (1.21 mumol/g) was determined in mouse brain 30 min after intraperitoneal administration of 5,5-dimethyl-delta 1-pyrroline (200 mg/kg). Neither methylGABA nor dimethylGABA penetrated into the central nervous system when administered in the periphery. The present studies suggest that pyrrolines may represent a chemical class of brain-penetrating precursors of pharmacologically active analogues of GABA.

Also, N-methyl- and N-acetyl-GABA are known to cross the BBB. Only the latter has ever been available, though no info exists on this compound.
Any thoughts as to synthesis or acquisition of any of these ?
SWIM is annoyed with the problems associated with synthesis of GBL/GHB.THF is too dangerous to store given the low flash point and combustibility and GABA is expensive and the intermediate creates a toxic gas as a byproduct. 1,4 BDO is as illegal as GHB for SWIM. The GABA analogs mentioned above are all still legal.

[blinkKDX]

this could work, but adding a methyl attachement often changes the effects of the chemical in the body.

[blinkKDX]

a good example, but on much different lines, is testosterone....great when injected. you can get test suspension, prop, eth., or cyp...

but when you take methyltestosterone you get a MUCH different effect. the adrogenic to anabolic ratio is changed.

its like 1ad...converts to 1testsosterone in the body, and is not too harsh on the body. on the other hand, methyl1testosterone is the most toxic, but one of the most, if not the most, potent oral steroids ever created. and to think, it was legal before the ban a few years ago.. and that happend because of careless people and too much info was out...

so another reason to keep RC's hush!!

[catfish_groid]

there is an analog of GABA called phenibut, AKA beta-phenyl GABA
but its activity has yet to be fully explored

[zera]

Check out a molecule called Baclofen, like GHB it's a ligand that binds to the GABA-B receptors and is not DEA scheduled. It was developed as a muscle relaxant for epilepsy, but is now used to treat spasticity. It is often administered into the spinal fluid, but is still orally active. It sounds like it has a lot of side effects at the upper end, but this might have to do with the exponential dose/response curve associated with GHB.

[snapper]

Reports on baclofen have been promising, but it is an rx drug and therefore problematic to source since SWIM does not suffer from muscle spasticity (thank god !). Here are some threads on the subject. SWIM wants something like what GBL was - a kick ass legal sedative/anxiolytic to regulate sleep. Baclofen sounds like it is speedy and poor for sleep. Otherwise it is intriguing. Perhaps a baclofen analog ?
Here are some links :

http://www.drugs-forum.com/forum/sho...light=baclofen

http://www.drugs-forum.com/forum/sho...light=baclofen

[darawk]

GHB exerts its effect by turning into GABA in the brain.

Are you certain about this? I thought they had recently disocvered GHB receptors that only GHB, and not GABA, bound to.

[snapper]

Perhaps SWIM incorrect or both mechanisms exist.
Any references? It would be interesting to clarify this point. SWIM'll try to locate refs for this as well, but if SWIY has'em handy, please share with the group ...