Amphetamine‐type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin

  title={Amphetamine‐type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin},
  author={Richard B. Rothman and Michael H. Baumann and Christina M. Dersch and D V Romero and Kenner C. Rice and F. Ivy Carroll and John S. Partilla},
A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine‐type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of release and inhibition of reuptake, respectively. If increases in NE mediate amphetamine‐type… 

Behavioral and neurochemical effects of amphetamine analogs that release monoamines in the squirrel monkey

The Effects of Amphetamine and Methamphetamine on the Release of Norepinephrine, Dopamine and Acetylcholine From the Brainstem Reticular Formation

The mechanistic approach followed here to describe the action of AMPHs within the RF is rooted on the fine anatomy of this region of the brainstem, and a number of reticular nuclei beyond classic DA mesencephalic cells are considered to extend the scenario underlying the neurobiology of AM PHs abuse.

Abuse-related effects of dual dopamine/serotonin releasers with varying potency to release norepinephrine in male rats and rhesus monkeys.

Comparing effects of four novel DA/5HT releasers that varied >800-fold in their selectivities suggests that potency to release NE has minimal influence on abuse liability of dualDA/5 HT releasers, and reducing relative potency torelease NE versus DA/ 5HT does not improve anticocaine efficacy.

Amphetamine maintenance differentially modulates effects of cocaine, methylenedioxypyrovalerone (MDPV), and methamphetamine on intracranial self-stimulation and nucleus accumbens dopamine in rats

The selective effectiveness of amphetamine maintenance to treat cocaine abuse may reflect attenuation of cocaine- induced increases in NAc DA while preserving cocaine-induced increases inNAc 5-HT.

Noradrenergic and dopaminergic effects of (+)‐amphetamine‐like stimulants in the baboon Papio anubis

The present data indicate that typical clinical doses of phentermine and (±)‐ephedrine may not release central DA in humans, a hypothesis that should ultimately be tested in controlled clinical studies.

Dopamine/serotonin releasers as medications for stimulant addictions.

Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction.

It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions, as well as for obesity, attention-deficit disorder, and depression.

Effects of “Legal X” Piperazine Analogs on Dopamine and Serotonin Release in Rat Brain

The hypothesis that the BZP/TFMPP combination mimics the neurochemical mechanism of MDMA, providing a basis for recreational use of these agents, is supported and the findings suggest possible drug‐drug synergism when piperazine drugs are coadministered at high doses.

Pharmacology, neurobiology and neurotoxicity of methamphetamine

Evidence of MA’s neurotoxic effects is presented to develop research strategies towards prospective designs looking at large cohorts of young people belonging to a risk group for recreational drug use.

Development of a Rationally Designed, Low Abuse Potential, Biogenic Amine Releaser That Suppresses Cocaine Self-Administration

The findings reported here demonstrate that nonamphetamine monoamine releasing agents such as PAL-287 might be promising candidate medications for the treatment of stimulant dependence.



Neurochemical neutralization of methamphetamine with high‐affinity nonselective inhibitors of biogenic amine transporters: a pharmacological strategy for treating stimulant abuse

An in vitro assay is established which selectively detects transporter substrates and used to profile the ability of a lead compound, indatraline, to block the releasing effects of METH and MDMA at the DA, 5‐HT, and NE transporters.

Dopamine ligands and the stimulus effects of amphetamine: animal models versus human laboratory data

Data regarding the effects of dopamine agonists and antagonists on the discriminative stimulus effects of amphetamine in animals and its subjective effects in humans are reviewed.

Subjective responses to d-amphetamine alone and after pimozide pretreatment in normal, healthy volunteers

High Dose Pimozide Does Not Block Amphetamine-Induced Euphoria in Normal Volunteers

  • L. BrauerH. Wit
  • Psychology, Biology
    Pharmacology Biochemistry and Behavior
  • 1997

The interaction of cocaine with serotonin dorsal raphe neurons. Single-unit extracellular recording studies.

  • K. CunninghamJ. Lakoski
  • Biology, Chemistry
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1990
The hypothesis that the inhibitory effects of cocaine on 5- HT DRN neurons are mediated by increased 5-HT available for interaction with5-HT1A impulse-regulating autoreceptors in the DRN is supported, as a consequence of cocaine-induced blockade of 5-ht reuptake processes.

Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man

This study suggests that it is unlikely that these central actions in man are a consequence of the release of norepinephrine in the brain, and suggests that these five agents share a common mode of central action.

Doses of GBR12909 that suppress cocaine self‐administration in non‐human primates substantially occupy dopamine transporters as measured by [11C] WIN35,428 PET scans

These data strongly suggest that occupancy for the DA transporter by GBR explains its ability to attenuate cocaine‐induced increases in extracellular DA and to suppress cocaine self‐administration and suggest that experimental human studies of orally administered GBR to test the DA hypothesis of cocaine addiction should use doses that produce at least 70% occupancy of theDA transporter.

Discriminative stimulus effects of d-amphetamine, methylphenidate and diazepam in humans