Tricyclic and Monoamine Oxidase Inhibitor Antidepressants: Structure-Activity Relationships

Maxwell, Robert A.; White, Helen L.

doi:10.1007/978-1-4613-4045-4_3

Cited by 10 publications

(8 citation statements)

References 148 publications

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“…Our data indicate that treatments known to alter extracellular NE also influence extracellular DA in mPFC . Most notably, local application of DMI, a drug that is highly selective for blocking the NE uptake carrier (Maxwell and White, 1978;Harms, 1983), increased extracellular DA as well as NE in rnPFC. Similarly, the selective a2 -adrenergic receptor antagonist idazoxan (Doxey et al ., 1983 ;Freedman and Aghajanian, 1984) increased the efflux of both NE and DA in mPFC .…”

Section: Discussionmentioning

confidence: 99%

Local Influence of Endogenous Norepinephrine on Extracellular Dopamine in Rat Medial Prefrontal Cortex

Gresch

Sved

Zigmond

et al. 1995

Journal of Neurochemistry

198

128

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Noradrenergic and dopaminergic projections converge in the medial prefrontal cortex and there is evidence of an interaction between dopamine (DA) and norepinephrine (NE) terminals in this region. We have examined the influence of drugs known to alter extracellular NE on extracellular NE and DA in medial prefrontal cortex using in vivo microdialysis. Local application of the NE uptake inhibitor desipramine (1.0 µM) delivered through a microdialysis probe increased extracellular DA (+149%) as well as NE (+201%) in medial prefrontal cortex. Furthermore, desipramine potentiated the tail shock‐induced increase in both extracellular DA (stress alone, +64%; stress + desipramine, +584%) and NE (stress alone, +55%; stress + desipramine, +443%). In contrast, local application of desipramine did not affect extracellular DA in striatum, indicating that this drug does not influence DA efflux directly. Local application of the α2‐adrenoceptor antagonist idazoxan (0.1 or 5.0 mM) increased extracellular NE and DA in medial prefrontal cortex. Conversely, the α2‐adrenoceptor agonist clonidine (0.2 mg/kg; i.p.) decreased extracellular NE and DA in medial prefrontal cortex. These results support the hypothesis that NE terminals in medial prefrontal cortex regulate extracellular DA in this region. This regulation may be achieved by mechanisms involving an action of NE on receptors that regulate DA release (heteroreceptor regulation) and/or transport of DA into noradrenergic terminals (heterotransporter regulation).

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Section: Discussionmentioning

confidence: 99%

Local Influence of Endogenous Norepinephrine on Extracellular Dopamine in Rat Medial Prefrontal Cortex

Gresch

Sved

Zigmond

et al. 1995

Journal of Neurochemistry

198

128

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“…The dihydrodibenzazepines differ from the dibenzocycloheptadenes by the presence of a nitrogen atom at the apex of the heterocyclic ring. The nitrogen atom is connected to the side chain by a single bond, which is believed to result in greater flexibility of the side chain (Maxwell & White, 1978). Table 1 summarizes the effects of these structural features on the interaction of these antidepressants with transport-P and with other pharmacological actions of these four antidepressants.…”

Section: Discussionmentioning

confidence: 99%

“…Exceptions to this rule are inhibition of the uptake of dopamine, in which the configuration of the amine is unimportant, and inhibition of the uptake of noradrenaline, in which secondary amines are more potent than tertiary amines (Table 1). The latter has led to the assumption that the amine-binding site of the noradrenaline transporter may lie within a relatively hydrophilic pocket (Maxwell & White, 1978).…”

Section: Discussionmentioning

confidence: 99%

Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport‐P) by tricyclic antidepressants

Al-Damluji

Kopin

1996

British J Pharmacology

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1 We have provided evidence for a novel amine uptake process for which prazosin is a substrate in postsynaptic neurones, characterized by a paradoxical increase in accumulation of the radioligand when the concentration of the unlabelled drug is increased above 10' M. This increase is due to activation of a proton-dependent, vacuolar type-ATPase-linked uptake process which is blocked by desipramine but is resistant to reserpine. We have now examined the effects of tricyclic antidepressants on this uptake system in a cell line derived from hypothalamic peptidergic neurones, known to be innervated by noradrenergic nerve terminals in vivo.2 [3H]-imipramine bound to the cells and was displaced by unlabelled imipramine, desipramine, amitriptyline and nortriptyline. The data fitted a single binding site model. This is the first demonstration of antidepressant binding sites in postsynaptic neurones. 3 There was no increase in the binding of [3H]-imipramine at high concentrations of unlabelled imipramine, suggesting that antidepressants inhibit uptake but are not themselves accumulated by peptidergic gonadotrophin releasing hormone neurones. 4 Accumulation of prazosin was competitively inhibited by antidepressants. Tertiary amines were slightly more potent than secondary amines and the presence of a nitrogen atom in the heterocyclic ring enhanced blocking activity. 5 The affinities of the antidepressants for the uptake process are within the range of plasma concentrations that are observed during therapeutic use of these compounds. Since it is likely that this uptake process has a physiological function, its inhibition by antidepressants may provide a new avenue for investigating the mechanism of action of these compounds.

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“…1976;Dc Paulis et al. 1978;Maxwell and White, 1978). Thus, the hNET and SERT cDNAs are likely to encode domains contributing common and distinct features of substrate and antagonist recognition.…”

mentioning

confidence: 99%

Molecular Biology and Functions of Carrier Proteins. Annual Symposium (46th) of the Society of General Physiologists held in Woods Hole, Massachusetts on September 10-13, 1992. Volume 48

Reuss¹,

Russell²,

Jennings³

1993

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Tricyclic and Monoamine Oxidase Inhibitor Antidepressants: Structure-Activity Relationships

Cited by 10 publications

References 148 publications

Local Influence of Endogenous Norepinephrine on Extracellular Dopamine in Rat Medial Prefrontal Cortex

Local Influence of Endogenous Norepinephrine on Extracellular Dopamine in Rat Medial Prefrontal Cortex

Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport‐P) by tricyclic antidepressants

Molecular Biology and Functions of Carrier Proteins. Annual Symposium (46th) of the Society of General Physiologists held in Woods Hole, Massachusetts on September 10-13, 1992. Volume 48

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