![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by myco on March 11, 2009, at 0:08:31
I'm not on Parnate but I found this study very interesting and not difficult to comprehend at all. Seems parnate does increase GABA. I know this may be old news for some of you but I liked it so here it is (MINUS the diagrams/graphs).Oh...is this kind of thing appreciated here? Does anyone actually read these big long 'copy to' studies that are occasionally posted on here or am I wasting my time?
myco
-------------------------------------------------------Eur Arch Psychiatry Clin Neurosci (2006) 256:268273
Helge Frieling & Stefan Bleich
Tranylcypromine
New perspectives on an old drugAbstract
The irreversible inhibitor of monoamine oxidase, tranylcypromine, is a potent antidepressant, but its use is limited to special indications due to side effects and dietary restrictions. The antidepressant action of tranylcypromine is not completely explainable by its effects on monoamine oxidase. Tranylcypromine also leads to an increase in brain trace amines, which are believed to play a key role in the pathophysiology of depression. It also affects other pathophysiological pathways associated with depression. Tranylcypromine treatment leads to an up-regulation of GABAB-receptors and modulates the phospholipid metabolism, which is essential for normal brain function. These findings implicate that the efficacy of tranylcypromine as an antidepressant may be due to its multiple actions within the human brain.
-------------------------------------------------------
Introduction
Non-selective monoamine oxidase (MAO) inhibitors (MAOI) like tranylcypromine (TCP) or phenelzine (PLZ) have proven to be potent and efficient antidepressants [47]. However, due to side effects and dietary restrictions, their use has been limited to therapyresistant depressions and atypical depressions with prominent neurovegetative symptoms [57]. At the introduction of the reversible MAO inhibitor Moclobemide (MOC), it was expected that a comparable antidepressive efficacy could be achieved with a favourable security profile [17]. In a recent metaanalysis, it has been shown that MOC is less effective than TCP or PLZ in the treatment of major depression [35]. This difference may not only be explainable by diverse binding-profiles to MAO isoforms since
mechanisms of drug action apart from MAO inhibition may contribute to the potency of TCP or PLZ. In the present work, the authors concentrate on possible effects of TCP on other neurochemical systems associated with depression or antidepressive actions.-------------------------------------------------------
Pharmacological profile of tranylcypromine
Tranylcyprominehemisulfate (MW: 364.46 g/mol) is a stereoisomeric substance with a structural analogy to amphetamine (Fig. 1). (+)-TCP mainly inhibits MAO while (-)-TCP interacts with monoamine-reuptake and release [54]. Both enantiomers exhibit markedly different pharmacokinetic properties such as plasma levels in humans and clearance rates from rat brains. Until recently, metabolic differences between the two enantiomers have not been investigated [25, 55, 59].
Metabolism
Following oral administration, TCP is rapidly absorbed and has a short elimination half-life of about2 h in humans [36]. It remains unclear, whether TCP is metabolized via opening of the cyclopropyl ring to amphetamine. Elevated levels of amphetamine and N-methylamphetamine have been observed in plasma samples of a patient ingesting 250 mg TCP [62]. Other researchers have been unable to demonstrate such conversion [29, 46]. Recently, it has been shown that opening of the cyclopropyl ring does not occur at usual doses of TCP [51]. Biotransformation of TCP seems to follow diverse ways: N-acetyl-TCP has been found in brain and urine of TCP-treated rats [12, 31] as well as 4-Hydroxy-TCP, the latter also being an inhibitor of MAO-A and B [3, 5]. TCP and its
metabolites are renally excreted.-------------------------------------------------------
Effects on neurotransmitter amines
The basic principle of the antidepressive action of TCP is an elevation of the catecholamines norepinephrine (NE) and dopamine (DA) and the indolealkylamine 5-hydroxytryptamine (5-HT, serotonin) by inhibiting the main enzymes of their degradation, the monoamine-oxidases A and B. However, treatment with TCP leads to an increase of activity of the semicarbazide sensitive amine oxidase (SSAO), another amine oxidase that metabolises NE, DA and 5-HT in different tissues, at least in rat hearts [18, 19]. Alterations in SSAO activity have been reported to be present in different psychiatric disorders [63]. Recently, we have found significantly lower plasma levels of SSAO in depressed patients when compared with healthy controls [65]. MAO and SSAO inhibition also leads to a marked increase of brain amines as tyramine (TYR), tryptamine (TRY), B-phenylethylamine
(B -PEA) and octopamine (OCT), which are termed trace amines (TA) because of their low
absolute concentrations in the brain relative to NE, DA or 5-HT. TAs can exert pharmacological effects: they can affect release or uptake of catecholamines and 5-HT at nerve endings [4, 44], and they seem to act as neuromodulators directly acting on catecholamine- or 5-HT-receptors [30, 43]. The interest in TA is mounting since the discovery of G-proteincoupled receptors for trace amines [8] and led to a rebirth of the PEA hypothesis of affective disorders. Briefly, a deficit of PEA that is postulated to be responsible for sustaining mood, physical energy and attention, or a deficit of PEA-turnover is proposed by several groups to be a causal factor for endogenous depression whereas an excess may lead to mania [14, 26]. Interestingly, PEA and phenylacetic acid (PAA), the main metabolite of PEA are metabolites of phenelzine (PLZ), another MAOI that is in clinical use as antidepressant [2]. TCP treatment leads to an increase of brain trace amines. However, the measured increase of PEA after MAO inhibition was not significantly correlated with improvement of depression [34]. Besides PEA, also TRY is discussed to be involved in the development of depression. Treatment with TCP and PLZ decreases the density of 3H-TRY-binding sites in rat brains. High doses of TCP lead to down-regulation of TCY-receptors in the hippocampus and striatum of rats [21, 39]. However, the clinical significance of these findings needs to be further clarified.
Trace amines and their receptors are discussed to be involved in different neuropsychiatric disorders such as psychosis and attention deficit and hyperkinetic disorder (reviewed in [9]), for some of those disorders casuistic data exist postulating a therapeutic effect of TCP.-------------------------------------------------------
Effects on receptors for amines and amino acids
Mainly the elevation of catecholamines and 5-HT seems to lead to changes in several pre- and postsynaptic receptors. Chronic administration of TCP lead to a down-regulation of B1- and B2-adrenoceptors in the rat brain cortex and other regions of the rat brain [20, 37, 38, 40, 52]. Some data exist proposing also a down-regulation of a1- and a2-receptors after chronic treatment with TCP in the rat brain [23]. Additionally, a decrease of 5-HT2-receptors was found after administration of high and low doses of TCP in rats [13, 21]. Furthermore, after chronic administration of TCP, a down-regulation of dopaminergic D1 and D2 receptors in the rat striatum was found [41].
y-Amino-butyric-acid is one of the neurotransmitters that have received considerable attention during the last years for their possible involvement in affective disorders. Studies using animal models of depression, radioligand binding and functional studies in rodent brain tissue and neuroendocrine challenge investigations implicate GABA in the pathophysiology of depression. However, these studies are not without conflicting findings [33, 58]. Chronic administration of TCP and some other antidepressants (PLZ, desipramine, fluoxetine) lead to a selectively increased expression of the GABAB(1a) subunit of the receptor in rats hippocampus. Only TCP leads also to an increase of the expression of GABAB(2) subunit. Treatment of rats with TCP significantly enhanced the response to baclofen, a GABAB- receptor agonist, in the hippocampal tissue and
leads to an increase of locomotor activity after amphetamine administration [49, 50].-------------------------------------------------------
Effects on enzymes other than MAO
Effects on cytochrome enzymesThe concomitant use of TCP and other drugs is restricted not only because of the elevated risk for hypertensive crisis or central serotonergic syndrome but also because of some possible interactions concerning cytochrome P 450 based drug degradation. Tranylcypromine is a potent inhibitor of CYP2A6 [15], CYP2E1 and, to a lesser extent, CYP1A2, CYP2C9, CYP2C19, CYP3A4 and CYP2D6. The effectiviy of CYP inhibition depends on the amino group of TCP. The non-amine homologue of TCP, cyclopropylbenzene, is a much less potent inhibitor of CYP1A2, CYP2A6, CYP2C19 and CYP2E1 activities and did not inhibit CYP2C9, CYP2D6 and CYP3A4 [56]. However, the inhibitory effects of TCP on the usual suspects for CYP-based drugdrug interaction, CYP2C9, CYP2C19 and CYP3A4 are not considered clinically relevant. During high-dose TCP therapy or in poor metabolizers of CYP2C19 substrates, clinically relevant interaction may occur [48].
CYP2A6 is the principle enzyme metabolizing nicotine to its inactive metabolite cotinine. It has been hypothesized that TCP may be useful to decrease smoking by inhibiting nicotine metabolism [64]. It has been well documented that the rate of cigarette smoking among psychiatric patient (e.g. depressed [10, 11, 16] or schizophrenia [60]) is significantly higher than in the general population. Smoking may reflect an attempt of self-medication [32], maybe by cigarette smoke mediated MAO inhibition [7]. The inhibitory effect of TCP on nicotine metabolism possibly contributes to its antidepressive effects. However, the relation between smoke, depression, MAO and TCP remains to be further clarified.-------------------------------------------------------
Effects on phospholipids and lipid-mediators
Recently, abnormalities in the metabolism of phospholipids have been implicated in the pathophysiology of depressive disorders. Phospholipids are essential for neuronal and synaptic structures and play key roles in the signal transduction response to different neurotransmitters [6]. Phospholipid derived mediators like prostaglandins, leukotrienes and thromboxanes are fundamental for many functions of the organism, e.g. the immune system. Especially, the role of poly-unsaturated fatty acids (PUFA) like omega-3 (w3) or omega-6 (w6) fatty acids and the x3/x6-ratio in the plasma membrane and lipid mediators has been widely investigated [24]. In depressed patients, an imbalance in PUFAs has been found with an excess of w6 acids like arachidonic acid (AA) and a deficiency of w3 fatty acids, such as eicosapentaenoic or docosahexaenoic acid. It was postulated that overactivity of different enzymes of the arachidonic cascade, like phospholipase A2 (PLA2) or coenzyme-A-independent transaminase (CoAIT) was underlying this imbalance, as diet did not seem to be its main cause [28]. CoAIT is of special interest, as this enzyme specifically affects only AA but not x3-fatty acids [61]. TCP is known to inhibit the release of AA from bradykinin-stimulated endothelial cells. It remains unclear, if this effect is due to PLA inhibition or if another enzyme is involved. It could be hypothesized that TCP inhibits CoAIT and therefore attenuates the w3/w6 imbalance by reducing the AA release. It is well known that lipid mediators derived from w3 fatty acids are more potent antiinflammatory and less potent proinflammatory agents than those derived from w6 fatty acids and may therefore excert positive effects on immune disturbances observed during depression [53]. Other effective antidepressive therapies like electroconvulsive therapy or lithium salts also affect the arachidonic cascade making the modulation of phospholipids an interesting target for novel antidepressants [1, 45].
TCP does not only affect AA release but also inhibits the prostacyclin synthase and therefore decreases the prostacyclin (PGI2) production [27]. Until recently, this property of TCP has not found attention in psychiatric research. PGI2 is one of the prominent endothelium derived vasodilating mediators [22, 42]. It is, therefore, surprising that TCP does neither have vasorelaxing nor vasoconstricting properties in vitro (Figs. 2 and 3), unlike other antidepressants (i.e. Amitriptyline) that lead to full relaxation of smooth muscles in vitro. This finding is of special interest, as
both agents lead to orthostatic hypotension as one of their main side-effects. In the case of TCP, it is unlikely to be mediated by peripheral effects of the drug, even though TCP interacts with different vasomotor controlling pathways.-------------------------------------------------------
Summary
Tranylcypromine is an efficient antidepressant. It does not only affect monoamine neurotransmitters by inhibiting the main enzymes of their degradation, MAO A and B, but is also implicated in several other pathophysiologic pathways, which have been associated with depression. TCP increases brain levels of trace amines, up-regulates GABAB-receptors and interferes with a variety of cytochrome P450 enzymes. TCP inhibits the release of arachidonic acid and prostacyclin, implicating diverse effects on inflammation, neuroplasticity and neurodegeneration. It is, therefore, not a selective inhibitor of monoaminoxidase, as the description MAOI may suggest. TCP is a somewhat dirty drug as it has a broad variety of effects. The most effective antidepressive treatments, however, affect more than one pathophysiological pathway. For further investigations in new antidepressants, a guideline may be the dirtier the better. Today, however, many of these dirty drugs come along with an unfavourable security profile or like TCP, drastic dietary restriction limiting there clinical use to special indications. Profound understanding of the pharmacologic profile of drugs like TCP may lead to more efficient and safe antidepressants in the future.
-------------------------------------------------------
References1. Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, Bukhman YV, Young TA, Charles V, Palfreyman MG
(2004) Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 24:2667
26772. Baker GB, Coutts RT, Greenshaw AJ (2000) Neurochemical and metabolic aspects of antidepressants: an overview. J Psychiat Neurosci 25:481496
3. Baker GB, Hampson DR, Coutts RT, Micetich RG, Hall TW, Rao TS (1986) Detection and quantitation of a ring-hydroxylated metabolite of the antidepressant drug tranylcypromine. J Neural Transm 65:233243
4. Baker GB, Martin IL, Mtichel PR (1977) The effects of some indolalkylamines on the uptake and release of 5-hydroxytryptamine in rat striatum [proceedings]. Br J Pharmacol 61:151P 152P
5. Baker GB, Urichuk LJ, McKenna KF, Kennedy SH (1999) Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 19:411426
6. Bazan NG (2003) Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid
Res 44:222122337. Berlin I, Said S, Spreux-Varoquaux O, Olivares R, Launay JM, Puech AJ (1995) Monoamine oxidase A and B activities in
heavy smokers. Biol Psychiat 38:7567618. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA 98:89668971
9. Branchek TA, Blackburn TP (2003) Trace amine receptors as targets for novel therapeutics: legend, myth and fact. Curr Opin Pharmacol 3:9097
10. Breslau N, Novak SP, Kessler RC (2004) Daily smoking and the subsequent onset of psychiatric disorders. Psychol Med 34:323 333
11. Breslau N, Novak SP, Kessler RC (2004) Psychiatric disorders and stages of smoking. Biol Psychiat 55:6976
12. Calverley DG, Baker GB, Coutts RT, Dewhurst WG (1981) A method for measurement of tranylcypromine in rat brain regions using gas chromatography with electron capture detection. Biochem Pharmacol 30:861867
13. Cohen RM, Ebstein RP, Daly JW, Murphy DL (1982) Chronic effects of a monoamine oxidase-inhibiting antidepressant: decreases in functional alpha-adrenergic autoreceptors precede the decrease in norepinephrine-stimulated cyclic adenosine
3˘:5˘-monophosphate systems in rat brain. J Neurosci 2:1588 159514. Davis BA, Boulton AA (1994) The trace amines and their acidic metabolites in depression an overview. Prog Neuropsychopharmacol Biol Psychiat 18:1745
15. Draper AJ, Madan A, Parkinson A (1997) Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch
Biochem Biophys 341:476116. Fergusson DM, Goodwin RD, Horwood LJ (2003) Major depression and cigarette smoking: results of a 21-year longitudinal study. Psychol Med 33:13571367
17. Fitton A, Faulds D, Goa KL (1992) Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness. Drugs 43:561596
18. Fitzgerald DH, Tipton KF (2002) Inhibition of monoamine oxidase modulates the behaviour of semicarbazide-sensitive
amine oxidase (SSAO). J Neural Transm 109:25126519. Fitzgerald DH, Tipton KF, Lyles GA (1998) Studies on the behaviour of semicarbazide-sensitive amine oxidase in
Sprague-Dawley rats treated with the monoamine oxidase inhibitor tranylcypromine. J Neural Transm Suppl 52:259
26420. Frazer A, Lucki I (1982) Antidepressant drugs: effects on betaadrenergic and serotonineregic receptors. Adv Biochem Psychopharmacol 31:6990
21. Goodnough DB, Baker GB (1994) Comparisons of the actions of high and low doses of the MAO inhibitor tranylcypromine on 5-HT2 binding sites in rat cortex. J Neural Transm Suppl 41:127134
22. Gordon JL, Pearson JD, MacIntyre DE (1979) Effect of prostaglandin E2 on prostacyclin production by endothelial cells.
Nature 278:48023. Greenshaw AJ, Nazarali AJ, Rao TS, Baker GB, Coutts RT (1988) Chronic tranylcypromine treatment induces functional alpha 2- adrenoceptor down-regulation in rats. Eur J Pharmacol 154:6772
24. Haag M (2003) Essential fatty acids and the brain. Can J Psychiat 48:195203
25. Hampson DR, Baker GB, Coutts RT (1986) A comparison of the neurochemical properties of the stereoisomers of tranylcypromine in the central nervous system. Cell Mol Biol 32:593599
26. Heller B, Fischer E, Martin R (1976) Therapeutic action of Dphenylalanine in Parkinsons disease. Arzneimittelforschung
26:577579
27. Hong SL, Carty T, Deykin D (1980) Tranylcypromine and 15- hydroperoxyarachidonate affect arachidonic acid release in
addition to inhibition of prostacyclin synthesis in calf aortic endothelial cells. J Biol Chem 255:9538954028. Horrobin DF (2001) Phospholipid metabolism and depression: the possible roles of phospholipase A2 and coenzyme
A-independent transacylase. Hum Psychopharmacol 16:455229. Jefferson JW (1992) Is tranylcypromine really metabolized to amphetamine? J Clin Psychiat 53:450451
30. Jones RS (1982) Tryptamine: a neuromodulator or neurotransmitter in mammalian brain? Prog Neurobiol 19:117139
31. Kang GI, Chung SY (1984) Identification of N-acetyl and hydroxylated N-acetyltranylcypromine from tranylcyprominedosed rat urine. Arch Pharm Res (Korea) 7:6568
32. Lerman C, Caporaso N, Main D, Audrain J, Boyd NR, Bowman ED, Shields PG (1998) Depression and self-medication with nicotine: the modifying influence of the dopamine D4 receptor gene. Health Psychol 17:5662
33. Lloyd KG, Zivkovic B, Scatton B, Morselli PL, Bartholini G (1989) The gabaergic hypothesis of depression. Prog Neuropsychopharmacol Biol Psychiat 13:341351
34. Locock RA, Baker GB, Coutts RT, Dewhurst WG (1984) Displacement of serotonin from binding sites in rat cortex: the
effects of biogenic trace amines. Prog Neuropsychopharmacol Biol Psychiat 8:70170435. Lotufo-Neto F, Trivedi M, Thase ME (1999) Meta-analysis of the reversible inhibitors of monoamine oxidase type A Moclobemide and brofaromine for the treatment of depression. Neuropsychopharmacology 20:226247
36. Mallinger AG, Edwards DJ, Himmelhoch JM, Knopf S, Ehler J (1986) Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects. Clin Pharmacol Ther 40:444450
37. McManus DJ, Greenshaw AJ (1991) Differential effects of chronic antidepressants in behavioural tests of beta-adrenergic
and GABAB receptor function. Psychopharmacology (Berl) 103:20420838. McManus DJ, Mousseau DD, Paetsch PR, Wishart TB, Greenshaw AJ (1991) Beta-adrenoceptors and antidepressants: possible 2-phenylethylamine mediation of chronic phenelzine effects. Biol Psychiat 30:11221130
39. Mousseau DD, McManus DJ, Baker GB, Juorio AV, Dewhurst WG, Greenshaw AJ (1993) Effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding to rat cortical membranes. Cell Mol Neurobiol
13:31340. Ordway GA, Gambarana C, Tejani-Butt SM, Areso P, Hauptmann M, Frazer A (1991) Preferential reduction of binding of
125I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments. J Pharmacol Exp Ther
257:68169041. Paetsch PR, Greenshaw AJ (1992) Effects of chronic antidepressant treatment on dopamine-related [3H]SCH 23390 and
[3H]spiperone binding in the rat striatum. Cell Mol Neurobiol 12:59760642. Parkington HC, Coleman HA, Tare M (2004) Prostacyclin and endothelium-dependent hyperpolarization. Pharmacol Res
49:50951443. Paterson IA, Boulton AA (1988) Beta-phenylethylamine enhances single cortical neurone responses to noradrenaline in
the rat. Brain Res Bull 20:17317744. Raiteri M, Del Carmine R, Bertollini A, Levi G (1977) Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur J Pharmacol 41:133143
45. Rapoport SI, Bosetti F (2002) Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder?
Arch Gen Psychiat 59:59259646. Reynolds GP, Rausch WD, Riederer P (1980) Effects of tranylcypromine stereoisomers on monamine oxidation in man. Br J Clin Pharmacol 9:521523
47. Riederer P, Lachenmayer L, Laux G (2004) Clinical applications of MAO-inhibitors. Curr Med Chem 11:20332043
48. Salsali M, Holt A, Baker GB (2004) Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6. Cell Mol Neurobiol 24:637649. Sands SA, Reisman SA, Enna SJ (2003) Effects of stress and tranylcypromine on amphetamine-induced locomotor activity
and GABA(B) receptor function in rat brain. Life Sci 72:10851092
50. Sands SA, Reisman SA, Enna SJ (2004) Effect of antidepressants on GABA(B) receptor function and subunit expression in rat hippocampus. Biochem Pharmacol 68:1489149551. Sherry RL, Rauw G, McKenna KF, Paetsch PR, Coutts RT, Baker GB (2000) Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine. J Affect Disord 61:2329
52. Sherry-McKenna RL, Baker GB, Mousseau DD, Coutts RT, Dewhurst WG (1992) 4-Methoxytranylcypromine, a monoamine oxidase inhibitor: effects on biogenic amines in rat brain following chronic administration. Biol Psychiat 31:881
88853. Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21:495505
54. Smith DF (1980) Tranylcypromine stereoisomers, monoaminergic neurotransmission and behavior. A minireview. Pharmakopsychiatr Neuropsychopharmakol 13:130136
55. Spahn-Langguth H, Hahn G, Mutschler E, Mohrke W, Langguth P (1992) Enantiospecific high-performance liquid chromatographic assay with fluorescence detection for the monoamine oxidase inhibitor tranylcypromine and its applicability
in pharmacokinetic studies. J Chromatogr 584:229 23756. Taavitsainen P, Juvonen R, Pelkonen O (2001) In vitro inhibition of cytochrome P450 enzymes in human liver microsomes by a potent CYP2A6 inhibitor, trans-2-phenylcyclopropylamine (tranylcypromine), and its nonamine analog, cyclopropylbenzene. Drug Metab Dispos 29:217222
57. Thase ME, Trivedi MH, Rush AJ (1995) MAOIs in the contemporary treatment of depression. Neuropsychopharmacology
12:18521958. Tunnicliff G, Malatynska E (2003) Central GABAergic systems and depressive illness. Neurochem Res 28:965976
59. Weber-Grandke H, Hahn G, Mutschler E, Mohrke W, LangguthP, Spahn-Langguth H (1993) The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers. Br J
Clin Pharmacol 36:36336560. Weiser M, Reichenberg A, Grotto I, Yasvitzky R, Rabinowitz J, Lubin G, Nahon D, Knobler HY, Davidson M (2004) Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiat 161:12191223
61. Winkler JD, Fonteh AN, Sung CM, Heravi JD, Nixon AB, Chabot-Fletcher M, Griswold D, Marshall LA, Chilton FH
(1995) Effects of CoA-independent transacylase inhibitors on the production of lipid inflammatory mediators. J Pharmacol
Exp Ther 274:1338134762. Youdim MB, Aronson JK, Blau K, Green AR, Grahame-Smith DG (1979) Tranylcypromine (Parnate) overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma. Psychol Med 9:377382
63. Yu PH (2001) Involvement of cerebrovascular semicarbazide- sensitive amine xidase in the pathogenesis of Alzheimers
disease and vascular dementia. Med Hypotheses 57: 17517964. Zhang W, Kilicarslan T, Tyndale RF, Sellers EM (2001) Evaluation of methoxsalen, tranylcypromine, and tryptamine as
specific and selective CYP2A6 inhibitors in vitro. Drug Metab Dispos 29:89790265. Ro¨ssner A, Weber A, Becker A, Beck G, Kornhuber J, Frieling H, Bleich S (2006) Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry (In Press)
Posted by Phillipa on March 11, 2009, at 0:10:26
In reply to Here's a study showing PARNATE upregulates GABA, posted by myco on March 11, 2009, at 0:08:31
Myco I usually read them. Love Phillipa
Posted by myco on March 11, 2009, at 0:20:42
In reply to Here's a study showing PARNATE upregulates GABA, posted by myco on March 11, 2009, at 0:08:31
This line in the summary makes the whole study:
"For further investigations in new antidepressants, a guideline may be the dirtier the better."
-Maoi users have got to love that! ;o) We're doytee boys n girls oh ya
Posted by desolationrower on March 11, 2009, at 1:50:30
In reply to Re: Here's a study showing PARNATE upregulates GABA » myco, posted by myco on March 11, 2009, at 0:20:42
Yes, several antidepressant affect gaba receptor expression. i had looked into GABAb agonists/antagonists a while ago, i don't think i ever made a post about it, they get complicated. no clear good/bad on what they do. GABAb seems to be frequently presynaptic auto&hetero receptors and extrasynaptic, and involved in tonic gaba levels.
-d/r
Posted by linkadge on March 13, 2009, at 17:57:22
In reply to Re: Here's a study showing PARNATE upregulates GABA, posted by desolationrower on March 11, 2009, at 1:50:30
This doesn't necessarily equate to increased gabaergic neurotransmission, however. The increase in gaba receptor activity may be an adaptive / homeostatic responce to the increase in synaptic neurotransmission caused by the antidepressant.
Linkadge
Posted by shasling on March 15, 2009, at 0:25:23
In reply to Re: Here's a study showing PARNATE upregulates GABA, posted by linkadge on March 13, 2009, at 17:57:22
> This doesn't necessarily equate to increased gabaergic neurotransmission, however. The increase in gaba receptor activity may be an adaptive / homeostatic responce to the increase in synaptic neurotransmission caused by the antidepressant.
>
> LinkadgeGotta tell ya,i posted many times on parnates new edition to addind this gaba b fact,and with no ill insult i have to say i dont understand what you mean with the above,in lamons term does this not mean that since parnate increases gaba b receptors then a gaba b drug such as the infamous ghb will likly be more potent to these parnate users?
Posted by JadeKelly on March 15, 2009, at 19:57:51
In reply to Re: Here's a study showing PARNATE upregulates GABA » myco, posted by myco on March 11, 2009, at 0:20:42
> This line in the summary makes the whole study:
>
> "For further investigations in new antidepressants, a guideline may be the dirtier the better."
>
> -Maoi users have got to love that! ;o) We're doytee boys n girls oh ya
myco,Wait....did you just call me "doytee" haha?
Thats right, the dirtier the better, as long as I'm feelin fine ;-)
btw-I thought the article was great. When you post those even if one person benefits...I think most people use a link, that may be why you're not used to seeing those long articles. Keep postin'
~Jade
Posted by myco on March 15, 2009, at 22:59:35
In reply to Re: Here's a study showing PARNATE upregulates GABA » myco, posted by JadeKelly on March 15, 2009, at 19:57:51
Yep i'm a doytee boy too lol :oP
Thanks for laughing though...there are only a handfull of us "laughers" or jokers on here...so nice to meet others. Balances out the misery ya know.
myco
75mg nardil-------------------
> > This line in the summary makes the whole study:
> >
> > "For further investigations in new antidepressants, a guideline may be the dirtier the better."
> >
> > -Maoi users have got to love that! ;o) We're doytee boys n girls oh ya
>
>
> myco,
>
> Wait....did you just call me "doytee" haha?
>
> Thats right, the dirtier the better, as long as I'm feelin fine ;-)
>
> btw-I thought the article was great. When you post those even if one person benefits...I think most people use a link, that may be why you're not used to seeing those long articles. Keep postin'
>
> ~Jade
Posted by JadeKelly on March 16, 2009, at 2:15:40
In reply to Re: Here's a study showing PARNATE upregulates GABA » JadeKelly, posted by myco on March 15, 2009, at 22:59:35
Jeez,
In the end I thought I was a dying breed, lol. Even in the suckiest mysery I have a sense of humor thank God. Search those people out, because the ones I found kept me going and when they left , well, it just was a bummer. Two friends from here I still email; I geuss we stay here as long as we need to and then its tempting to leave for good. But I think I will come back every now and then to see if I can help someone. Because someone helped me. I was here for 5 months and stalked for a couple months before that. Obviously this community offers somthing to people who aren't there yet. And If I get sick again, I hope someone will welcome me back.
~Jade
Posted by JadeKelly on March 16, 2009, at 2:20:10
In reply to Re: Here's a study showing PARNATE upregulates GABA » JadeKelly, posted by myco on March 15, 2009, at 22:59:35
This is the end of the thread.
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