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Dr. Bob is Robert Hsiung, MD,
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Posted by JohnL on December 2, 2000, at 5:56:12
I don't quite follow this technical stuff. But this research abstract tends to imply to me that somehow the alpha-1 and dopamine D2 chemistries are interrelated.
Perhaps somewhere in this complicated chemistry it might be explained why Adrafinil + Amisulpride works well for me? Adrafinil=alpha1, Amisulpride=D2.
Any comments or explanations from the technical experts out there?
Thanks,
John
1: Psychopharmacology (Berl) 1990;101(1):62-6
Related Articles, Books
Effects of single and repeated treatment with
antidepressants on apomorphine-induced yawning in
the rat: the implication of alpha-1 adrenergic
mechanisms in the D-2 receptor function.Delini-Stula A, Hunn C
Research Laboratories, CIBA-GEIGY Ltd., Basle, Switzerland.
Acute (10 or 20 mg/kg IP) and subchronic (2 x 5 or 10 mg/kg IP daily for
7 days) effects of desipramine, imipramine, maprotiline, (+)- and
(-)-oxaprotiline enantiomers as well as selective 5-HT-uptake inhibitors
citalopram and ifoxetine on yawning, induced by low doses of
apomorphine, were investigated in the rat. In addition, the effects of
alpha-1 receptor agonist adrafinil and antagonist prazosin were also
tested. After acute treatment, desipramine, the stereoselective NA-uptake
inhibiting (+)-enantiomer of oxaprotiline, and the alpha-1 agonist adrafinil,
markedly and significantly suppressed yawning. Prazosin, in contrast,
clearly potentiated it. This potentiating effect was abolished by the
pretreatment with (+)-oxaprotiline and adrafinil. Other drugs were
inactive. After subchronic administration, yawning was antagonized by
NA-uptake-inhibiting antidepressants, including imipramine and
maprotiline. By comparison to the acute treatment, the inhibitory effects
of desipramine and (+)-oxaprotiline were considerably enhanced. Neither
selective 5-HT-uptake inhibitors nor (-)-oxaprotiline (levoprotiline) were
active. Antidepressants therefore modulate the functional activity of D-2
receptors, activated by low doses of apomorphine, predominantly by the
virtue of their noradrenergic enhancing properties. This modulatory effect
appears to be mediated by alpha-1 adrenergic receptors.PMID: 1971448, UI: 90260109
Posted by AndrewB on December 4, 2000, at 10:00:41
In reply to alpha-1 and D2 related? , posted by JohnL on December 2, 2000, at 5:56:12
John,
Thank you for posting this interesting abstract. It is established that both serotnergic and andrenergic ADs upregulate postsynaptic D2 receptor activity. This increase in D2 (D3?) activity possibly is ultimately responsible for the mood elevating properties of these ADs.
One thing that is interesting in this study is that they achieved the D2 effect with alpha-1 agonism within a week but not with 5-HT uptake inhibitors. Serotonergic drugs take some time usually (2 weeks plus) to exhibit their mood benefit. Likewise these serotenergic drugs take some time to upregulate the D2 receptors. The reason for this seems to be that the serotonergic system does not act directly on the D2 receptors but rather via modulating the NMDA receptors which in turn modulate the D2 receptors.
This study suggest that there may be a rather direct connection between the alpha1 system and the D2 receptors.BTW, I've been very interested lately in the NMDA system's involvement in D2/D3 modulation. It seems that, in some cases at least, NMDA dyregulation is resposible for AD non-response or poop out. It seems likely that lithium's ability to modulate NMDA activity (via control of calcium influx) explains it effectiveness as an augmentation agent to ADs. This to me points to the potential usefullness other drugs that modulate NMDA activity. For example, memantine modulates NMDA activity via control of calcium influx like lithium but without any of lithium's nasty side effects (lithium is a dirty drug).
Again thanks for the posting,
AndrewB
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