Posted by SLS on December 4, 2000, at 23:01:35
In reply to Mazindol and amineptine are very different, posted by Bradley on December 4, 2000, at 14:31:17
> Mazindol is a CNS stimulant and amineptine is a dopamine reuptake inhibitor.
They are both stimulants. They are both dopamine reuptake inhibitors. Neither is an amphetamine.
One of the reasons why amineptine was withdrawn was because it was used by athletes to enhance performance in place of amphetamine, which had been banned. Eventually, amineptine became a banned substance and was routinely tested for before athletic events. Of course, it was the amphetamine-like addictive potential of amineptine that dissuaded psychiatrists from using it routinely. Many doctors never thought much of it to begin with. I think amineptine was probably a great tool to have in a psychiatric armementarium for polypharmacy, and, like so many other crappy drugs (e.g. moclobemide), was a miracle for some people.
> Still looking for alternatives to amineptine.
You may want to take a closer look at mazindol. Early in its development, the assays used at the time showed it to potently inhibit the reuptake of dopamine as well as norepinephrine. It was initially studied as an antidepressant. Current literature still regards mazindol to be a dopamine reuptake inhibitor and studies use it as such. It is one of the most potent binders and markers of the DA transporter (the protein complex that functions as the reuptake carrier). Mazindol might be an interesting choice to combine with amisulpride.
- Scott
--------------------------------------------------------2: J Psychopharmacol 1999;13(3):300-7
Do antidepressants have any potential to cause addiction?
Haddad P
Moorside, Trafford General Hospital, Davyhulme, Manchester, UK.
Addiction/dependence is a syndrome in which the hallmark is a compulsive pattern of drug use. Most authorities do not regard antidepressants as causing addiction but this has been challenged. This debate is explored drawing on case reports and related clinical and pharmacological data. An extensive literature review identified 21 English language case reports of antidepressant addiction (DSM-IV 'substance dependence' criteria) published since 1963. Sixteen involved tranylcypromine or amineptine and may reflect their dopaminergic and stimulant properties. Subject characteristics included male sex (14/21), personality problems (10/21) and prior substance misuse (14/21). Withdrawal or discontinuation symptoms have long been recognized with antidepressants but other features of addiction such as tolerance and compulsive use are exceptionally rare. Common clinical problems are patients taking subtherapeutic dosages and prematurely stopping antidepressants. The pharmacodynamic profiles of most antidepressants and the absence of acute 'desirable' effects make addiction theoretically unlikely. It is concluded that, with the exception of tranylcypromine and amineptine, antidepressants do not have a clinically significant liability to cause addiction. Tranylcypromine and amineptine should be avoided in those with a history of substance misuse. Patients prescribed other antidepressants should be told that they are not addictive.
Publication Types:
Review
Review, tutorialPMID: 10512092, UI: 99440643
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"The MDMA-induced increase in the extracellular concentration of both dopamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamine uptake inhibitor."5: J Neurochem 1999 Jun;72(6):2516-22
Mazindol attenuates the 3,4-methylenedioxymethamphetamine-induced formation of hydroxyl radicals and long-term depletion of serotonin in the striatum.
Shankaran M, Yamamoto BK, Gudelsky GA
College of Pharmacy, University of Cincinnati, Ohio 45267-0004, USA.
The formation of hydroxyl radicals following the systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) was studied in the striatum of the rat by quantifying the stable adducts of salicylic acid and D-phenylalanine, namely, 2,3-dihydroxybenzoic acid (2,3-DHBA) and p-tyrosine, respectively. The repeated administration of MDMA produced a sustained increase in the extracellular concentration of 2,3-DHBA and p-tyrosine, as well as dopamine. The MDMA-induced increase in the extracellular concentration of both dopamine and 2,3-DHBA was suppressed in rats treated with mazindol, a dopamine uptake inhibitor. Mazindol also attenuated the long-term depletion of serotonin (5-HT) in the striatum produced by MDMA without altering the acute hyperthermic response to MDMA. These results are supportive of the view that MDMA produces a dopamine-dependent increase in the formation of hydroxyl radicals in the striatum that may contribute to the mechanism whereby MDMA produces a long-term depletion of brain 5-HT content.
PMID: 10349862, UI: 99277365
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" Pretreatment with mazindol, a dopamine uptake inhibitor, was without effect on peripheral metabolism of [(11)C]-(S)-nicotine."3: Synapse 1999 Nov;34(2):124-34
Pharmacokinetics of radiotracers in human plasma during positron emission tomography.
Cumming P, Yokoi F, Chen A, Deep P, Dagher A, Reutens D, Kapczinski F, Wong DF, Gjedde A
McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada. paul@pet.auh.dk
Many radiopharmaceuticals for positron emission tomography (PET) are substantially metabolized in peripheral organs. Pharmacological treatments intended to alter cerebral metabolism might also alter radiotracer metabolism, consequently altering the cerebral uptake. First-order rate constants for the metabolism of PET tracers can be calculated by a linear graphical method from the precursor and metabolite concentrations measured in plasma extracts fractionated by HPLC. We tested the effects of specific pharmacological challenges on the plasma kinetics of six tracers used for PET studies of neurotransmission. The rate of O-methylation of circulating [(18)F]fluorodopa, a tracer of dopa decarboxylase activity in brain, was unaffected by pretreatment with amantadine, an antagonist of glutamate receptors. [(11)C]Deprenyl, a tracer of monoamine oxidase activity, was rapidly metabolized to [(11)C]methamphetamine and polar metabolites in healthy volunteers. The net rate constant of this metabolism was three times higher in a group of subjects under treatment for epilepsy, consistent with induction of hepatic microsomal enzymes by antiepileptic drugs. [(11)C]Sch 23390, a ligand for dopamine D1 receptors, was rapidly metabolized to polar metabolites. The net rate constant of metabolism was unaffected by pretreatment with lorazepam. [(11)C]-(S)-Nicotine, a ligand for nicotinic receptors, was rapidly metabolized to [(11)C]-(S)-cotenine, which is less polar than the parent compound. Pretreatment with mazindol, a dopamine uptake inhibitor, was without effect on peripheral metabolism of [(11)C]-(S)-nicotine. [(11)C]WIN 35,428, a tropane derivative which labels dopamine uptake sites, was metabolized to a nonpolar metabolite, but so slowly that the rate constant of this process could not be calculated. [(11)C]Raclopride, a ligand for dopamine D2 receptors, was first metabolized to a nonpolar metabolite, which then yielded two hydrophilic metabolites. The initial metabolic step was substantially blocked by pretreatment with amphetamine, possibly indicative of competitive inhibition of microsomal oxidation. Together, these results indicate that the linear graphic method is useful for estimating the kinetics of the plasma metabolism of many widely used PET tracers. Drug-drug interactions were revealed in subjects treated with specific pharmacological agents prior to tracer administration.
Copyright 1999
Wiley-Liss, Inc.PMID: 10502311, UI: 99432305
poster:SLS
thread:49708
URL: http://www.dr-bob.org/babble/20001130/msgs/49933.html