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Re: tremors, lithium, mechanisms » danf

Posted by SLS on July 8, 2000, at 8:28:05

In reply to tremors, posted by danf on July 7, 2000, at 22:42:49

Dear DanF,

On behalf of the folks here, I just want to thank you for your relevant and knowledgable input. I don't know if you had been a participant on Psycho-Babble before I arrived here (10/99), but I value your presence now.


> kerry, You a burden.. never !
>
> now for tremors !

How very exciting!

> tremor is usually mediated by the adrenergic system. both zyprexa & lithium can cause this. with zyprexa being the likely culprit ( incidence increases with dose increases). irritability is a manefestation of anxiety & anxiety also drives tremor as I can well attest to. so anxiety may be part of the tremor.


In Re: Tremor stuff

In the past, some doctors would rely upon hand tremors as a clinical indicator of therapeutic dosages of lithium. They would adjust the dosage to the minimum that would produce them, the tremors being barely noticeable.

Question: In what ways are Zyprexa-induced tremors different from lithium-induced tremors? How are they produced? Along with the fine hand tremors, I noticed a cog-wheel effect when I lifted weights while taking lithium.


In Re: Heuristic stuff

Much of what lithium does to exert its therapeutic effects are not understood. It does so many things. You've got me curious to review some of the mechanisms by which it affects membrane potentials and electrolyte pumps. Perhaps I should save my energy and let you review them for me. :-) (half-serious). One of the things that has been studied is the effects lithium has on postsynaptic second-messenger systems, particularly protein kinase-C (PKC). I believe there is some speculation that this ultimately results in changes in gene expression. It also inhibits glycogen synthase kinase 3 beta (GSK-3 beta), which leads to the production of both neurotrophic and neuroprotective substances (MAP1B-P and bcl-2 respectively). Lithium also directly inhibits membrane receptor G-protein activity, which might help to explain its immediate antimanic effects. I think I remember an NIH doctor tell me that lithium also changes the expression of G-proteins through c-FOS mediated gene transcription, but my memory is vague on this.


- Scott


-----------------------------------------------


Found this on Medline:


13: Aust N Z J Psychiatry 1999 Dec;33 Suppl:S65-83

Signalling pathways in the brain: cellular transduction of mood stabilisation in
the treatment of manic-depressive illness.

Manji HK, McNamara R, Chen G, Lenox RH

Department of Psychiatry, Wayne State University School of Medicine, Detroit,
Michigan 48201, USA. hmanji@med.wayne.edu

The long-term treatment of manic-depressive illness (MDI) likely involves the
strategic regulation of signalling pathways and gene expression in critical
neuronal circuits. Accumulated evidence has identified signalling pathways, in
particular the family of protein kinase C (PKC) isozymes, as targets for the
long-term action of lithium. Chronic lithium administration produces a reduction
in the expression of PKC alpha and epsilon, as well as a major PKC substrate,
MARCKS, which has been implicated in long-term neuroplastic events in the
developing and adult brain. More recently, studies have demonstrated robust
effects of lithium on another kinase system, GSK-3beta, and on
neuroprotective/neurotrophic proteins in the brain. Given the key roles of these
signalling cascades in the amplification and integration of signals in the
central nervous system, these findings have clear implications not only for
research into the neurobiology of MDI, but also for the future development of
novel and innovative treatment strategies.

Publication Types:
Review
Review, tutorial

PMID: 10622182, UI: 20085894

 

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