Effect of long term amineptine treatment on pre‐ and postsynaptic mechanisms in rat brain

Ceci, Angelo; Garattini, Silvio; Gobbi, Marco; Mennini, Tiziana

doi:10.1111/j.1476-5381.1986.tb09495.x

Cited by 25 publications

(5 citation statements)

References 24 publications

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“…Amineptine displays moderate affinity for DAT and low affinity for both NET and SERT ( Table 1 ). In screening assays with a concentration up to 10 μ M, amineptine did not bind to 5-HT 1A , 5-HT 2A , D 2 , α 1 , α 2 , H 1 , benzodiazepine, or gamma-aminobutyric acid (GABA) sites [ 327 ]. The chemical structure of amineptine is illustrated in Figure 4 .…”

Section: Dat Inhibitorsmentioning

confidence: 99%

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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The motor manifestations of Parkinson's disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia.

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Section: Dat Inhibitorsmentioning

confidence: 99%

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Huot

Fox

Brotchie

2015

Parkinson's Disease

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“…Another mechanism common to most TCA is an increase in dopaminergic transmission. This is unexpected as most AD, with the exception of amineptine, do not affect DA uptake in vitro or after acute administration in vivo (Ceci et al 1986 ;Garattini & Mennini, 1989). The explanation includes increased sensitivity of postsynaptic DA receptors (Spyraki & Fibiger, 1981) and decreased sensitivity of pre-synaptic DA receptors (Serra et al 1979).…”

Section: Chronic Effectmentioning

confidence: 96%

Antidepressant agents: from tricyclics to serotonin uptake inhibitors

1998

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“…Amineptine was approved in France for severe clinical depression of endogenous origin in 1978, and use has been suggested in Parkinson’s disease, amotivational syndromes and ADHD (Deniker et al, 1981). In addition to inhibition of DAT, amineptine is a releaser of dopamine (Bonnet et al, 1987; Ceci et al, 1986). Hepatotoxicity (Lazaros et al, 1996), along with the potential for abuse (Bertschy et al, 1990; Castot et al, 1990; Haddad, 1999), led to the suspension of the French marketing authorization for amineptine in 1999.…”

Section: Role Of Dopamine In the Pathophysiology Of Mddmentioning

confidence: 99%

Antidepressant drug development: Focus on triple monoamine reuptake inhibition

Lane

2014

J Psychopharmacol

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Many patients with major depressive disorder (MDD) only partially respond, and some have no clinically meaningful response, to current widely used antidepressant drugs. Due to the purported role of dopamine in the pathophysiology of depression, triple-reuptake inhibitors (TRIs) that simultaneously inhibit serotonin (5-HT), norepinephrine (NE) and dopamine reuptake could be a useful addition to the armamentarium of treatments for MDD. A TRI should more effectively activate mesolimbic dopamine-related reward-networks, restore positive mood and reduce potent 5-HT reuptake blockade associated "hypodopaminergic" adverse effects of decreased libido, weight gain and "blunting" of emotions. On the other hand, dopaminergic effects raise concern over abuse liability and TRIs may have many of the cardiovascular effects associated with NET inhibition. Several clinical development programs for potential TRI antidepressants have failed to demonstrate significantly greater efficacy than placebo or standard of care. Successful late-stage clinical development of a TRI is more likely if experimental research studies in the target population of depressed patients have demonstrated target engagement that differentially and dose-dependently improves assessments of reward-network dysfunction relative to existing antidepressants. TRI treatment could be individualized on the basis of predictive markers such as the burden of decreased positive mood symptoms and/or neuroimaging evidence of reward network dysfunction. This review focuses on how the next generation of monoamine-based treatments could be efficiently developed to address unmet medical need in MDD.

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Effect of long term amineptine treatment on pre‐ and postsynaptic mechanisms in rat brain

Cited by 25 publications

References 24 publications

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Monoamine Reuptake Inhibitors in Parkinson’s Disease

Antidepressant agents: from tricyclics to serotonin uptake inhibitors

Antidepressant drug development: Focus on triple monoamine reuptake inhibition

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