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  • 1
    Electronic Resource
    Electronic Resource
    Inhibition of Aromatic L-Amino Acid Decarboxylase and Tyrosine Aminotransferase by the Monoamine Oxidase Inhibitor Phenelzine (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 46 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The concentration of p-tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p-tyramine levels in the first 1–2 h following injection. The high dose of phenelzine increased the p-tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p-tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine amino-transferase activity of rat liver homogenates; the IC50 was 50 μM. Phenelzine also inhibited the aromatic L-amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 μM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L-amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p-tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p-tyramine levels followed later by very large increases in p-tyramine levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb08511.x
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  • 2
    Electronic Resource
    Electronic Resource
    Potentiation of the behavioural effects of the antidepressant phenelzine by deuterium substitution (1983)
    Springer
    Psychopharmacology 81 (1983), S. 122-125 
    Details
    ISSN: 1432-2072
    Keywords: Phenelzine ; Deuterium substitution ; Behaviour ; Potentiation ; Monoamine oxidase inhibition ; Antidepressant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phenelzine in the rat induced biphasic behavioural stimulation, which was profoundly potentiated by deuterium substitution. Doses of 12.5 or 25.0 mg/kg phenelzine had little or no effect on spontaneous activity, whereas the same doses of deuterated phenelzine produced hyperactivity, wetdog shakes, forepaw padding, splayed hind limbs, backward walking, sniffing and stereotyped grooming 2–12 h after injection. Similarly, the behavioural response induced by 50.0 mg/kg phenelzine was strongly potentiated by deuterium substitution. It appears likely that the increased behavioural response induced by deuterated phenelzine may be due to its greater potency as a monoamine oxidase inhibitor compared to undeuterated phenelzine. Since phenelzine is an antidepressant that is particularly efficacious in the treatment of severe anxiety, a deuterated analogue of the drug seems likely to be clinically useful.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429005
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  • 3
    Electronic Resource
    Electronic Resource
    Involvement of brain trace amines in the behavioural effects of phenelzine (1988)
    Springer
    Neurochemical research 13 (1988), S. 113-119 
    Details
    ISSN: 1573-6903
    Keywords: Phenelzine ; brain trace amines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The MAO inhibitor phenelzine (PLZ) at a dose of 25 mg/kg does not affect the behavior of rats. In contrast, the equivalent dose of a deuterated analog (α,α,β,β-tetradeutero-PLZ, d4PLZ) elicits a biphasic behavioral syndrome in rats. In an attempt to correlate changes in cerebral monoamines with behavior, the concentration of various amines were measured at various times after the administration of either d4PLZ or PLZ (25 mg/kg). In general, PLZ and d4PLZ caused elevations in brain amine levels, particularly in the time period 2–12 hours after drug administration. Furthermore, d4PLZ increased the concentrations of serotonin (5-HT), phenylethylamine (PE), tryptamine (T),meta-tyramine (mTA), and 3-methoxytyramine (3-MT) to a greater extent than PLZ. Since the time course of behavioral excitation closely parallels the elevations in T and PE levels in the brain and since the percentage increases in PE and T levels following d4PLZ compared to PLZ treatment were substantially greater than those of the other amines, it was postulated that PE and T are involved in d4PLZ-induced behaviors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00973322
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  • 4
    Electronic Resource
    Electronic Resource
    The in vitro release of endogenousm-tyramine,p-tyramine and dopamine from rat striatum (1982)
    Springer
    Neurochemical research 7 (1982), S. 705-716 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Administration of phenelzine (100 mg/kg, i.p., 18 hr) increased rat striatal concentrations of pTA, mTA and DA by 30, 6.7 and 1.5 fold, respectively. Lesions of the medial forebrain bundle prevented these increase, permitting the conclusion that the phenelzine-induced amine increases were localized in the synaptic terminals. The release of endogenous pTA, mTA and DA from striatal slices obtained from phenelzine-treated rats was investigated. 50 mM KCl elicited releases of pTA, mTA and DA which were significantly greater than their respective basal releases. These K+-stimulated releases were antagonized significantly by 15 mM MgCl2, suggesting that they are calcium-dependent in nature. We have concluded, therefore, that mTA and pTA, as well as DA, are released from striatal nerve terminals in vivo. The total amounts of mTA and DA, but not pTA, released in the release experiments were greater than those found in the nonincubated tissue. It appears, therefore, that the biosynthesis of mTA and DA was stimulated during the incubation of the striatal slices.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00965523
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of antidepressant drugs on inositol phospholipid hydrolysis in rat cerebral cortical slices (1989)
    Springer
    Neurochemical research 14 (1989), S. 1047-1052 
    Details
    ISSN: 1573-6903
    Keywords: Inositol phosphates ; antidepressants ; noradrenaline ; α1-antagonists ; phosphoinositide hydrolysis ; tricyclics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of several different types of antidepressant drugs on phosphoinositide hydrolysis by slices of rat cerebral cortex was investigated by prelabeling inositol phospholipids with [3H]inositol and then measuring the formation of [3H]inositol phosphates (a total fraction consisting of the mono-and poly-phosphates was collected) in the presence of 10 mM LiCl. All of the drugs tested (amitriptyline, trimipramine, mianserin, desipramine, tranylcypromine, and citalopram) inhibited NE-stimulated [3H]inositol phosphate formation. This inhibition appeared to be due to antagonism of α1-receptors. In addition to inhibiting the effects of NE, the tricyclic antidepressants themselves were able to stimulate [3H]inositol phosphate formation. This stimulation occurred at drug concentrations higher than that needed to inhibit stimulation by NE. Stimulatory effects of the antidepressants themselves were not blocked by the α1-antagonist, prazosin. An examination of the types of inositol phosphates formed revealed that formation of inositol monophosphate was stimulated, but that inostiol biphosphate production was decreased by tricyclic antidepressants compared to control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00965609
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  • 6
    Electronic Resource
    Electronic Resource
    Tryptamine transport in rat brain slices: A comparison with 5-hydroxytryptamine (1984)
    Springer
    Neurochemical research 9 (1984), S. 617-628 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The uptake of [14C]tryptamine (14C-T) and [3H]serotonin (3H-5HT) into slices of rat hypothalamus (HT), fronto-parietal cortex (CX), and caudate nucleus (Cau) has been investigated. In all three brain areas, the uptake of3H-5HT at 37°C was much greater than that in an ice-bath at 1.0–1.5°C. In contrast, the uptake of14C-T at 37°C was not much greater than uptake at 1.0–1.5°C. While markedly different amounts of3H-5HT were accumulated by each of the brain areas studied, the regional uptake of14C-T was quantitatively similar. In general the uptake of14C-T was inhibited less than3H-5HT by cocaine, DNP, ouabain, and decreased Na+ concentrations. Similarly,14C-T was less susceptible to serotonin uptake inhibitors except in the caudate. It was concluded that though a common indoleamine uptake system accumulates both T and 5HT, a non-specific low affinity or diffusional process also transports both amines and is predominantly responsible for T, but not 5HT, uptake. The spontaneous release, or wash-out, of14C-T from the caudate was much faster than that of3H-5HT. In addition, while depolarizing stimuli caused little or no release of14C-T, large releases of3H-5HT were observed. T, therefore, does not behave like a conventional neurotransmitter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00964508
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  • 7
    Electronic Resource
    Electronic Resource
    Uptake ofpara-tyramine andmeta-tyramine into slices of the caudate nucleus and hypothalamus of the rat (1979)
    Springer
    Neurochemical research 4 (1979), S. 633-642 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The kinetics of the uptake ofp-tyramine,m-tyramine, and dopamine were investigated in slices of the hypothalamus and striatum of the rat in the presence of nialamide. When uptake was analyzed by a least-squares fit to a Lineweaver-Burk plot, each amine appeared to be concentrated by both a “low”-affinity and a “high”-affinity system in both brain regions. The obtainedK m andV max values for the “high”-affinity uptake system for each amine in both brain regions were similar. In general terms, the uptake systems in the striatum exhibited largerK m andV max values, with the velocity of uptake being in the order dopamine〉m-tyramine〉p-tyramine. 2,4-Dinitrophenol (DNP) and ouabain reduced all uptakes in the caudate, but reduced only the “high”-affinity uptake ofm-tyramine and the “low”-affinity uptake of dopamine in the hypothalamus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00964440
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  • 8
    Electronic Resource
    Electronic Resource
    Uptake and release ofmeta-tyramine,para-tyramine, and dopamine in rat striatal slices (1978)
    Springer
    Neurochemical research 3 (1978), S. 775-791 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The uptakes of high-affinity concentrations (10−8 M) ofmeta-tyramine (m-TA),para-tyramine (p-TA), and dopamine (DA) into rat striatal slices have been shown to be inhibited by DNP and ouabain. We now demonstrate that cocaine (5×10−6 M) and low concentrations of sodium ion (26×10−3 M) also reduced these uptakes. The spontaneous efflux and the release [induced by an elevated concentration of potassium ion (5×10−2 M)] of each of the previously accumulated amines were studied in the presence and absence of added calcium ions. The spontaneous efflux of each amine (especially the tyramines) was enhanced by the absence of calcium ions. Part of this enhancement seemed to be due to an inhibition of a calcium-dependent reuptake. The elevated concentration of potassium ion proved to be an effective releaser of each amine; and for DA, such release was decreased by the removal of calcium. Form- andp-TA, however, the removal of calcium either did not reduce or completely abolished the releases depending upon the duration of the calcium removal. The significance of these findings is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00966000
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  • 9
    Electronic Resource
    Electronic Resource
    Release of radiolabeled dopamine,p-tyramine, andm-tyramine from rat striatal slices by some aminotetralins (1981)
    Springer
    Neurochemical research 6 (1981), S. 365-375 
    Details
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of several 2-aminotetralins (2ATs) on the uptake and release of [14C] dopamine and [3H]m- or [3H]p-tyramine by rat striatal slices was examined. 6,7-Dihydroxy-2AT (6,7OHAT) and 5,6-dihydroxy-2-methyl-AT (5,6OHMeAT) were the most potent uptake inhibitors as well as the most potent releasers of the three labeled amines. The 5-, 6-, and 7-hydroxy-2-N,N-dipropyl-ATs (5-, 6-, and 7OHdiPrAT) and 5,6-dihydroxy-2-N,N-dipropyl-AT (5,6OHdiPrAT) significantly inhibited the uptakes of the three labeled amines, but they released only the tyramines. The dipropyl substitution of a 2AT appeared to confer a tyraminergic specificity to its release properties. To verify this supposition, 2AT was compared to 2-N,N-dipropyl-AT (diPrAT). Although 2AT released both [3H]p-tyramine and [14C]dopamine, diPrAT released only [3H]p-tyramine. None of the compounds, however, differentiated betweenm- andp-tyramine. It was concluded that the release of tyramines could be implicated in the actions of some of the 2ATs and that the tyramines can be transported independently from dopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00963851
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