GBR 12909 stimulation compared to cocaine

[Alfa]

Relationship between in vivo occupancy at the dopamine transporter and behavioral effects of cocaine, GBR 12909 [1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine], and benztropine analogs.

Medication Discovery Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

Analogs of benztropine (BZT) bind to the dopamine (DA) transporter and inhibit DA uptake but often have behavioral effects that differ from those of cocaine and other DA-uptake inhibitors. To better understand these differences, we examined the relationship between locomotor-stimulant effects of cocaine, 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)-piperazine (GBR 12909), and BZT analogs [(3alpha-[bis(4'-fluorophenyl)methoxy]-tropane) (AHN 1-055) and (N-allyl-3alpha-[bis(4'-fluorophenyl)methoxy]-tropane) (AHN 2-005)] and their in vivo displacement of the DA transporter ligand [125I]3beta-(4-iodophenyl)-tropan-2beta-carboxylic acid isopropyl ester hydrochloride (RTI-121) in striatum. Cocaine, GBR 12909, and BZT analogs each displaced [125I]RTI-121 and stimulated locomotor activity in a dose- and time-dependent manner. The time course revealed a slower onset of both effects for AHN 1-055 and AHN 2-005 compared with cocaine and GBR 12909. The BZT analogs were less effective than cocaine and GBR 12909 in stimulating locomotor activity. Locomotor stimulant effects of cocaine were generally greater than predicted by the regression of displacement of [125I]RTI-121 and effect at short times after injection and less than predicted at longer times after injection. This result suggests that the apparent rate of occupancy of the DA transporter, in addition to percentage of sites occupied, contributes to the behavioral effects of cocaine. The present results suggest that among drugs that act at the DA transporter, the slower apparent rates of occupancy with the DA transporter by the BZT analogs may contribute in an important way to differences in their effectiveness.

[Alfa]

All in all this means that the motor stimulation that GBR 12909 gives is comparable to that of cocaine, while leaving other effects unrevealed.

[nanobrain]

any info on this one being tried in man? what about GBR 12783? that one seems even more interesting with an almost total selectivity for DA vs NE.

[u4ic]

Hell yeah. It's all about the dopamine, baby!

[Iggypoop]

Hell yeah and the possible psychosis it might create!!!

[Bio-Cellular Enigma]

Originally Posted by Iggypoop

Hell yeah and the possible psychosis it might create!!!

SWIM wonders if that is what 'scares off' some RC sellers, in terms of dopaminergic compounds (e.g. MDPV). Although this potential does exist, SWIM is not aware of any stories actually making the news with compounds in that category. SWIM thinks it's likely that (A) many people will self-limit prior to psychosis, due to its extreme unpleasantness, and (B) even if it does occur, it will tend not to get 'advertised' or reported in emergency rooms and such... not enough media hype.

As long as the compound is safe enough in terms of not causing death, SWIM feels it will stay out of the news. To him, that means something that plays well with other substances (particularly alcohol) and has a low overall toxicity. It's always the stories of teens collapsing and being taken to the ER that make the headlines. Psychosis seems very unlikely to do so, not to mention it's nearly always a passing event that (while highly unpleasant and disruptive) isn't truly dangerous.

[toe]

Any speculations on what that might mean for 3α-carbomethoxy-4β-(4-chlorophenyl)-N-methylpiperidine aka
(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidine-3-carboxylate

Which I was reading about here?