Posted by Larry Hoover on June 27, 2004, at 14:17:17
In reply to Wheeeee - SAM-eeeee, posted by Emme on June 27, 2004, at 6:59:26
> Wow. Dang. This stuff kicks a stimulating punch. Very buzzy/speedy. I can see the potential for hypomania. My brain seems to be unable to settle in and focus, but it's awfully nice to have a (very) clean house and not be crying. I'm trying cutting it down to 50 mg.
>
> Can anyone tell me its mechanisms of action? All I know at the moment is that it's a methyl group donor for neurotransmitter sythesis.The only problem with that concept is that there is no (major) neurotransmitter that is formed via methylation. Adrenaline (epinephrine) is formed by methylation of noradrenaline (norepinephrine), but adrenaline is not generally thought of as central nervous system active.
I suspect that this idea of methylation of neurotransmitter sythesis arises from a theoretical neurotransmitter, dubbed "barinine", which was proposed in 1989. No evidence for a substance like barinine has ever been found, yet the myth persists.
SAMe performs many functions, but is most likely involved in improving phospholipid turnover in neuronal membranes, and in the synthesis of sulphur-bearing amino acids creatine and cysteine. As such, it would likely be most effective when used with lecithin, and would be complementary to fish oil.
Here are some abstracts which show the variety of mechanisms which are associated with SAMe. Interestingly enough, some of those effects are gender-specific.
Lar
J Psychiatr Res. 1990;24(2):177-84.Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant.
Fava M, Rosenbaum JF, MacLaughlin R, Falk WE, Pollack MH, Cohen LS, Jones L, Pill L.
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
S-adenosyl-L-methionine (SAMe), a putative antidepressant, is a naturally occurring substance whose mechanism of action is still a matter of speculation. It has been recently postulated that SAMe may increase the dopaminergic tone in depressed patients. Since dopamine inhibits both thyrotropin (TSH) and prolactin secretion, we investigated the effects of treatment with SAMe on the TSH and prolactin response to thyrotropin-releasing-hormone (TRH) stimulation in 7 depressed outpatient women (mean age: 46.1 +/- 7.2 years) and 10 depressed outpatient men (mean age: 38.0 +/- 10.0 years) participating in a six-week open study of oral SAMe in the treatment of major depression. At the end of the study, there was a significant reduction after treatment with SAMe in the response of both prolactin and TSH to TRH stimulation in the group of depressed men compared to pre-treatment values. On the other hand, in the group of depressed women, the posttreatment prolactin response to TRH did not appear to change when compared to pre-treatment and the TSH response to TRH challenge tended even to augment slightly after treatment with SAMe. Our results, at least in depressed men, seem to support the hypothesis of a stimulating effect of SAMe on the dopaminergic system.
Drugs. 1990;40 Suppl 3:98-110.Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease.
Chawla RK, Bonkovsky HL, Galambos JT.
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.
Am J Med. 1987 Nov 20;83(5A):95-103.Neuropharmacology of S-adenosyl-L-methionine.
Baldessarini RJ.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
The metabolite S-adenosyl-L-methionine (SAMe), when prepared as the stable p-toluene-sulfonate complex of its sulfate salt and given parenterally in high doses, appears to have mood-elevating effects in depressed adults. The material is remarkably well tolerated when given by injection or intravenous infusion for this purpose, even in elderly or demented patients. Assuming that the toluene sulfonate component is inert, SAMe appears to have central neuropharmacologic effects after systemic injection in high doses. Nevertheless, the functional consequences of these remain unclear and, indeed, the ability of exogenous SAMe to reach the brain, and especially neuronal cytoplasm, is limited. SAMe has small effects on monoamine metabolism and, after injection, appears to have effects on the microviscosity of cell membranes that may be related to stimulation of phospholipid synthesis. The recent introduction of an orally administered form of SAMe for use in the treatment of osteoarthritis promises to stimulate further study of SAMe in disease-associated depression, major depressive disorder, and other neuropsychiatric conditions.
Psychiatry Res. 1986 Feb;17(2):111-8.Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers.
Sherer MA, Cantoni GL, Golden RN, Rudorfer MV, Potter WZ.
S-adenosyl-methionine (SAMe) is currently undergoing trials as a possible antidepressant. Because SAMe's mechanism of action is obscure and norepinephrine (NE) is often implicated in affective disorders, we studied the effects of SAMe on this neurotransmitter in volunteers. Plasma NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the supine and standing position were studied before and after acute placebo or a single 400 mg dose of SAMe and following seven daily administrations; concomitant measures were heart rate (HR) and blood pressure. Subjects were unable to distinguish acute drug from placebo, and although chronic SAMe administration was open, they reported no behavioral effects. Standing HR and plasma NE were reduced following chronic SAMe. Qualitatively similar changes are obtained following chronic treatment with monoamine oxidase inhibitors (MAOIs). However, unlike MAOIs, chronic SAMe treatment was not associated with changes in plasma MHPG. Exaggerated standing NE is found in depressed patients; SAMe may reduce this abnormal response, providing a clue for its mechanism of action in depression.
Am J Clin Nutr. 2002 Nov;76(5):1148S-50S.
S-Adenosylmethionine: molecular, biological, and clinical aspects--an introduction.Lieber CS, Packer L.
Section of Liver Disease and Nutrition, Bronx VA Medical Center, Mount Sinai School of Medicine, NY 10468, USA. liebercs@aol.com
In clinical research, a novel approach has emerged: some of the essential nutrients are being used to treat pathologic conditions. Many of these nutrients, including methionine, must first be activated in the liver or in other tissues before they can exert their key functions. However, this activating process is impaired in disease states and, as a consequence, nutritional requirements change. For instance, for methionine to act as the main cellular methyl donor, it must first be activated to S-adenosylmethionine (SAMe; also known as ademethionine). SAMe is required and is of fundamental importance for the metabolism of nucleic acids and polyamines, the structure and function of membranes, and as a precursor of glutathione. These processes are often seriously altered in various pathologic states addressed in this symposium, but they cannot be restored by simply administering methionine. For instance, in liver disease associated with impairment of the enzyme that activates methionine to SAMe, supplementation with methionine is useless and may even become toxic as it accumulates because it is not used. Accordingly, one must correct the lack of SAMe by bypassing the deficiency in enzyme activation; this is done by providing the product of the defective reaction, namely SAMe. Under these pathologic conditions, SAMe becomes crucial for the functioning of the cell. Thus SAMe, which is found in all living organisms, becomes the essential nutrient instead of methionine. This symposium reviewed the biological and corresponding molecular aspects of SAMe metabolism and the clinical consequences of its deficiency or supplementation in various tissues.
poster:Larry Hoover
thread:360892
URL: http://www.dr-bob.org/babble/alter/20040613/msgs/361003.html