11 replies to this topic

[happy santa]

Hello are there any supplements, or ways of raising dopamine only, without raising adrenergics (epinephrine, norepinephrine) or cortisol at the same time? The reason is I tried uridine, but I got too anxious and overaroused. Not very unsurprising since uridine breaks down to choline in the body, and choline increases dopamine and also --> epinephrine. Do you know any herb or a safe supplement with a "cleaner" dopamine effect without the anxiety and adrenergic action?

[AlexCanada]

Is uridine safe w modafinil?  I reallyy need something for dopamine. Lack of emotion, and general lack of arousal, lack of pleasure I been feeling so much these days. 

[Speculosity]

If Uridine is too much for you, try CDP choline.

I have somewhat of the same problem, uridine makes me feel sort of miserable, but CDP choline (which has uridine in it) works fine. It increases dopamine in the striatum.

It doesn't make me feel more pleasure per se, but it does increase my motivation without there being a stimulant feeling.

[happy santa]

What about catuaba? I heard its a good herb that has not too strong stimulating effect

[gamesguru]

Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms

• Acute oral treatment with the extract of T. catigua produced antidepressant-like effects in the forced swimming model in both mice and rats. Anti-immobility actions of T. catigua extract in mice were significantly reversed by haloperidol or by chlorpromazine, but not by pimozide, ketanserin, spiroxatrine or p-chlorophenylalanine. In vitro, T. catigua extract concentration-dependently inhibited the uptake and increased the release of serotonin, and especially of dopamine, from rat brain synaptosomal preparations.

Mucuna^[1]

Rhodiola (MAO-B)

Inducers of PH (phenylalanine hydroxylase):

Lamiaceae^[1]

Simple diet^[2]

Exercise^[3]

Iron^[4]

High ORAC foods^[5]

 

Inducers of TH (tyrosine hydroxylase):

Horny goat weed^[1]

Lithium

Ginkgo

Bacopa^[2]

Green tea^[3]

 

Upregulators of receptors (dopamine):

Caffeine^[1]

Bacopa^[2]

Exercise^[3]

 

[Area-1255]

Well OP - dopamine is converted into norepinephrine by means of the enzyme dopamine-Beta-hydroxylase  - so your goal would be to suppress activation of that enzyme ... 

http://www.oalib.com...27#.VfBWKxFViko

It's also a copper-dependent enzyme...so in theory, Zinc and Magnesium could help raise basal and stimulated DA release by opposing actions on Copper-dependent pathways.

Another idea.

 

J Antibiot (Tokyo). 1980 Apr;33(4):435-40.

Inhibition of dopamine-beta-hydroxylase, A copper enzyme, by bleomycin.

Matsui H, Kato T, Yamamoto C, Takita T, Takeuchi T, Umezawa H, Nagatsu T.

Abstract

Bleomycin was found to be one of the most potent inhibitors of dopamine-beta-hydroxylase. Bleomycin-A2 at 8 X 10(-8) M inhibited the enzyme activity by 50%. Kinetic studies showed that the inhibition by bleomycin-A2 was of the competitive type with both the substrate and the cofactor, ascorbate, and was not affected by fumarate, a stimulator for the enzyme. The inhibition mechanism is possibly due to chelating action of bleomycin toward the copper atom at the active site of the enzyme together with some other kinds of binding, for the addition of the cupric ions or extensive dialysis completely reversed the inhibition and bleomycin Cu(II)-complex did not inhibit the enzyme.

 

PMID:   6157665   [PubMed - indexed for MEDLINE]    Free full text

Opposing Role of Dopamine D1 and D2 Receptors in Modulation of Rat Nucleus Accumbens Noradrenaline Release

 

 

D1-receptors tend to stimulate norepinephrine release ; whereas D2R-autoreceptor activation tends to decrease it...it also has a lot to do with the cAMP-pathways.

 

Specifically 5-HT7-G-protein coupled +cAMP pathways, 5-HT7 receptors are stimulatory serotonin receptors which not only act to inhibit GABA release (which would then lead to anxiety and other issues) but also prevent or attenuate inhibition BY GABA of serotonergic neurons..this leads to incremental increases of serotonin which contribute to norepinephrine release..

 

 

Neuropharmacology. 2004 Jun;46(7):935-41.

GABAergic modulation of 5-HT7 receptor-mediated effects on 5-HT efflux in the guinea-pig dorsal raphe nucleus.

Roberts C1, Thomas DR, Bate ST, Kew JN.

Author information

 

Abstract

5-HT(7) receptor mRNA and protein are localised in the dorsal raphe nucleus (DRN) on non-serotonergic neurones. The effect of 5-HT(7) receptor antagonism on 5-HT efflux was measured from guinea-pig DRN slices, using the technique of fast cyclic voltammetry. The 5-HT(7) receptor antagonist, SB-269970-A, significantly inhibited 5-HT efflux. The GABA(A) receptor agonist, muscimol, significantly inhibited 5-HT efflux, to a similar degree as SB-269970-A. In contrast, the GABA(A) receptor antagonist, bicuculline, significantly increased 5-HT efflux and attenuated the muscimol-induced inhibition. The muscimol and SB-269970-A effects were not additive and in the presence of bicuculline the SB-269970-A-induced inhibition of 5-HT efflux was attenuated. These data suggest that 5-HT(7) receptor antagonist-induced inhibition of 5-HT efflux occurs indirectly via activation of GABA(A) receptors. That is, 5-HT(7) receptors may be located on GABA interneurones and when activated decrease GABA release and hence decrease the inhibitory tone on 5-HT neurones, increasing 5-HT efflux in the DRN. Therefore, in the presence of GABAergic tone 5-HT(7) receptor antagonists would decrease 5-HT release from the DRN.

PMID:   15081790   [PubMed - indexed for MEDLINE]

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

 

 

 

So in summary, a good idea would be..

 

• Zinc and Magnesium at night.
• Other possible methods of inhibiting DBH would be regulating histamine release.
• There are some herbal remedies which have been shown to inhibit DBH; such as St.John's Wort, however, they may not be the best option for ya - so do your research!
• D2-agonists medications wouldn't actually help raise dopamine - but they would decrease norepinephrine to an extent. 
• 5-HT7 antagonists; such as Amisulpride could help, but they would have to be stacked with a dopamine agonist in order to prevent prolactin accumulation which would have negative effects on DA terminals and release rates/

 

 

Biochem Biophys Res Commun. 2015 Mar 13;458(3):584-9. doi: 10.1016/j.bbrc.2015.02.009. Epub 2015 Feb 11.

Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.

Murakami M1, Yoshikawa T2, Nakamura T2, Ohba T3, Matsuzaki Y4, Sawamura D4, Kuwasako K5, Yanagisawa T6, Ono K3, Nakaji S7, Yanai K2.

Author information

 

Abstract

The histamine system is involved in the regulation of the autonomic nervous system. We used gene-targeted mice to investigate the role of histamine receptors in the regulation of the sympathetic nervous system. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed histamine H1, H2, and H3 receptor expression in the superior cervical ganglion, which contains sympathetic nerve cell bodies. We measured the heart rate variability (HRV), the changes in the beat-to-beat heart rate, which is widely used to assess autonomic activity in the heart. H1 blockade attenuated the baroreflex-mediated changes in heart rate in wild-type (WT) mice, whereas the heart rate response to H2- and H3-specific blockers was unaffected. l-Histidine decarboxylase (HDC) expression in the superior cervical ganglion of H1R-null mice was higher than that in WT controls, whereas the enzyme levels in H2R- and H3R-null mice were not significantly different from those in the WT. All mutant mice (H1R-, H2R-, and H3R-null mice) showed normal electrocardiogram (ECG) patterns with little modification in ECG parameters and the expected response to the β-adrenergic blocker propranolol. Similar to our findings in WT mice, H1 blockade attenuated the baroreflex-mediated heart rate change in H1R-null mice, whereas the heart rate response was unaffected in H2R- and H3R-null mice. The HRV analysis revealed relatively unstable RR intervals, an increased standard deviation of the interbeat interval (SDNN), and low-frequency (LF) component in H1R-null mice compared with the other groups, suggesting that sympathetic nerve activity was altered in H1R-null mice. Taken together, our findings indicate that H1 receptors play a major role in the regulation of sympathetic nerve activity.

Copyright © 2015 Elsevier Inc. All rights reserved.

KEYWORDS:

Autonomic nerves; ECG; Histamine; Mouse; Sympathetic nerves

Arzneimittelforschung. 1999 Feb;49(2):106-9.

Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase.

Kleber E1, Obry T, Hippeli S, Schneider W, Elstner EF.

Author information

 

Abstract

Extracts from the herb "St. John's wort" (Hypericum perforatum L.) are used for the treatment of mental depression, nervousness, sleeplessness and for their wound healing, diuretic and antirheumatic properties. As one biochemical mechanism for depression lack of catecholamine neurotransmitters has been discussed. The results of this investigation show that alcoholic extracts from Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine-beta-hydroxylase with an IC50 of 0.1 mu mol/l; pure commercial hypericin inhibits with an IC50 of 21 mu mol/l. Enzymes involved in the synthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by hypericin at concentrations from 1 up to 10 mu mol/l.

PMID:   10083977   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 09 September 2015 - 04:12 PM.

[gamesguru]

So in summary, a good idea would be..

• Zinc and Magnesium at night.
• Other possible methods of inhibiting DBH would be regulating histamine release.
• There are some herbal remedies which have been shown to inhibit DBH; such as St.John's Wort, however, they may not be the best option for ya - so do your research!
• D2-agonists medications wouldn't actually help raise dopamine - but they would decrease norepinephrine to an extent. 

Might 5-HT2Cs^[1] be a connection between fatigue and plant-based diet^[2]?  It would seem at least a contributing factor if dopamine beta-hydroxylase is copper-dependent.

Interesting about histamine's role.

 

Ginseng is a D2 agonist, and I found this:

 

"Ginsenosides Rb2, Rd and Rg1 significantly decreased norepinephrine and/or epinephrine-induced increase of IL-6 level in macrophage cell"

"Results: Panax ginseng and diazepam both per se did not modify NE levels of brain and hypothalamus in unstressed rats. But both the drugs attenuated stress-induced elevation of NE of brain and hypothalamus and simultaneously attenuated stress-induced elevation of plasma corticosterone."

 

------conflicting studies------

"Ginseng root saponins (200mg/kg by intraperitoneal injection) inhibited the decrease of brain 5-HT and noradrenaline and the increase in serum corticosterone and in heat-stresssed mice but the dopamine level was unchanged."

"The favorable effects of ginseng on learning and memory processes were also demonstrated in aged rats.15  In some cases, the memory-improving effect of ginseng especially at low doses, was more pronounced in old rats than in young rats.  The effect of ginseng on cognition was accompanied by the ginseng-induced increase in the levels of dopamine and noradrenaline and a decrease in the serotonin level in the hippocampus.15  Watanabe et al. reported that chronic feeding with 1% red ginseng powder resulted in significant increase in D-2 receptors in aged rats.16,17 "

[Area-1255]

Good point as well my friend!

 

 

So in summary, a good idea would be..

• Zinc and Magnesium at night.
• Other possible methods of inhibiting DBH would be regulating histamine release.
• There are some herbal remedies which have been shown to inhibit DBH; such as St.John's Wort, however, they may not be the best option for ya - so do your research!
• D2-agonists medications wouldn't actually help raise dopamine - but they would decrease norepinephrine to an extent. 

Might 5-HT2Cs^[1] be a connection between fatigue and plant-based diet^[2]?  It would seem at least a contributing factor if dopamine beta-hydroxylase is copper-dependent.

Interesting about histamine's role.

 

Ginseng is a D2 agonist, and I found this:

 

"Ginsenosides Rb2, Rd and Rg1 significantly decreased norepinephrine and/or epinephrine-induced increase of IL-6 level in macrophage cell"

"Results: Panax ginseng and diazepam both per se did not modify NE levels of brain and hypothalamus in unstressed rats. But both the drugs attenuated stress-induced elevation of NE of brain and hypothalamus and simultaneously attenuated stress-induced elevation of plasma corticosterone."

 

------conflicting studies------

"Ginseng root saponins (200mg/kg by intraperitoneal injection) inhibited the decrease of brain 5-HT and noradrenaline and the increase in serum corticosterone and in heat-stresssed mice but the dopamine level was unchanged."

"The favorable effects of ginseng on learning and memory processes were also demonstrated in aged rats.15  In some cases, the memory-improving effect of ginseng especially at low doses, was more pronounced in old rats than in young rats.  The effect of ginseng on cognition was accompanied by the ginseng-induced increase in the levels of dopamine and noradrenaline and a decrease in the serotonin level in the hippocampus.15  Watanabe et al. reported that chronic feeding with 1% red ginseng powder resulted in significant increase in D-2 receptors in aged rats.16,17 "

 

 

[happy santa]

Any ways to increase dopamine levels in the prefrontal cortex? And not the striatum? I.e via the mesocortical tracts and not mesolimbic tracts. I heard norepinephrine increases dopamine levels in the PFC (which it does via the mesocortical tracts), and that is the only simplest way I heard of increasing dopamine in that area. But since I have issues with anxiety and stress, norepinephrine will not help me with this issue, so I was wondering if there are some other possibilities available. I want this because I want to increase my cognition and analytical/logical mind, and not pleasure/motivational mind, per se.

Edited by happy santa, 01 February 2016 - 08:55 PM.

[Zed]

Any ways to increase dopamine levels in the prefrontal cortex? And not the striatum? I.e via the mesocortical tracts and not mesolimbic tracts. I heard norepinephrine increases dopamine levels in the PFC (which it does via the mesocortical tracts), and that is the only simplest way I heard of increasing dopamine in that area. But since I have issues with anxiety and stress, norepinephrine will not help me with this issue, so I was wondering if there are some other possibilities available. I want this because I want to increase my cognition and analytical/logical mind, and not pleasure/motivational mind, per se.

 

Have you considered any intra nasal med? such as insulin..or some of the newer peps?
 

[gamesguru]

I heard norepinephrine increases dopamine levels in the PFC

u wot m8

 

somewhere you should be able to find a list of DBH inhibitors (that's the enzyme for hydrolyze dopamine down to NE).  can't recall off the top of my head, but ginseng, wheat, and st johns were all on the list.  decreasing the ratio of dietary copper to zinc also works, because the enzyme is copper dependent and zinc is a convenient modulator of the NE transporter

 

 

Edited by gamesguru, 16 June 2017 - 12:58 AM.

[Jiminy Glick]

Rhodiola Rosea Salidroside perhaps?