|
| ||
|
||
|
| ||
|
||
 |
|
|
|
Contents Page 1 |
At low doses Meridia (sibutramine) seems to have few side effects (1), however, at high doses (60 mg) it has been shown to raise blood pressure (2). In one study, 6 out of 21 people taking 20 mg reported having stimulant-type problems (1). Side effects are minor at low doses but, unfortunately, low doses are less effective for weight loss (1, 3). Long-term effectiveness seems to require a dosage of about 30 mg (3). George Bray, who is one of the top obesity researchers, is optimistic about Meridia (3). That is definitely a good sign. Meridia inhibits the reuptake of noradrenaline (NA) and serotonin (3). A good part of its appetite suppressing effect seems to be the result of alpha 1 receptor stimulation since the administration of a drug that blocks the alpha 1 receptors eliminated the hypophagic (appetite reducing) effect of Meridia (4). A drug that blocks the beta 1 receptors was found to reduce, but not eliminate, the appetite suppressing effect of Meridia (4). Also, Meridia has been found to cause an "18 fold increase in brown adipose tissue glucose utilization" (5). |
|
|
|
If It Looks Like A Duck, And....The side effects of this drug and its stimulation of brown fat should tell you something about it. Lets see now, only doses that produce stimulant-type side effects are effective for long-term weight loss (3) and people report sleep difficulties (1). Hello? Sound familiar? In case you haven't figured it out, the scientists have let the cat out of the bag: Meridia is a THERMOGENIC drug (5, 6). It's not only a thermogenic drug -- it has other modes of action -- but if you want it to be effective for long-term weight loss you have to take a dose that produces thermogenesis and ECA-like side effects. Meridia increases thermogenesis in rats for at least six hours (5). It is quite possible that taking Meridia twice per day would be the most effective method since this would mimic the sustained thermogenic effect that people get by taking three doses of ECA per day. People have taken Meridia (sibutramine) twice per day as an antidepressant (7). It also seems that one could start out with a low dose of Meridia and gradually work up to a dose that is sufficient for long-term weight loss (3). Unfortunately, there is not a lot of data on the long-term safety of high dosages of Meridia. Whatever dose one ends up taking, a gradual approach could minimize the stimulant side effects because the beta-1 receptors will downregulate (8). Downregulation occurs with regular use of drugs that stimulate beta receptors (9). Just read the literature on asthma drugs. With ECA I started with a quarter dose and took two months to work up to my full dose (25 mg ephedrine and 200 mg caffeine) three times a day. I also take one enteric-coated 81 mg aspirin per day. It is not smart to take more than that. A simple (but logical) rule of thumb: if it is unpleasant, take less. Don't be in a hurry. I no longer feel any stimulation from ECA but the fat burning continues. |
|
|
|
MONA LISADon't let anyone tell you that the thermogenic effect of obesity drugs is of minor importance. Nothing could be further from the truth. Reduced thermogenesis is one of the primary metabolic defects that cause obesity. In obesity, the sympathetic nervous system (SNS) puts out insufficient noradrenaline (NA). This results in insufficient stimulation of the beta receptors and cripples your ability to breakdown and burn fat. Thus, you become fat. This metabolic defect is the bull's-eye. I mean no offense, but if you don't understand the importance of thermogenesis you have missed the target and your dart is stuck in the wall somewhere. It really is that important.
If you think I'm exaggerating, do a MEDLINE search and find out what thermogenesis and MONA LISA is all about (10). George Bray invented the MONA LISA (11-NA) acronym that means: Most Obesities kNnown Are
(MONA) In fact, George Bray has stated that for obesity to occur, reduced thermogenesis (mediated by the sympathetic nervous system) is required, however, "increased food intake itself can produce obesity, but it is usually not essential" (10). Thermogenesis sounds pretty darned important to me -- even more important than how much I eat. I wonder why the medical industry hasn't been telling us about this? |
|
|
|||
|
Written |
1.) Weintraub, M, Rubio, A, Golik, A, Byrne, L, and Scheinbaum, ML "Sibutramine in weight control: a dose-ranging, efficacy study." Clin Pharmacol Ther 1991 Sep, Vol 50 (3), Pg 330-7, PMID: 0001914367. 2.) King, DJ and Devaney, N "Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers." Br J Clin Pharmacol 1988 Nov, Vol 26 (5), Pg 607-11, PMID: 0003207566. 3.) Ryan, DH, Kaiser, P, and Bray, GA "Sibutramine: a novel new agent for obesity treatment." Obes Res 1995 Nov, Vol 3 Suppl 4, Pg 553S-559S, PMID: 0008697058. 4.) Jackson, HC, Bearham, MC, Hutchins, LJ, Mazurkiewicz, SE, Needham, AM, and Heal, DJ "Investigation of the mechanisms underlying the hypophagic effects of the 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat." Br J Pharmacol 1997 Aug, Vol 121 (8), Pg 1613-8, PMID: 0009283694. 5.) Stock, MJ "Sibutramine: a review of the pharmacology of a novel anti-obesity agent." Int J Obes Relat Metab Disord 1997 Mar, Vol 21 Suppl 1, Pg S25-9, PMID: 0009130038. 6.) Weiser, M, Frishman, WH, Michaelson, MD, and Abdeen, MA "The pharmacologic approach to the treatment of obesity." J Clin Pharmacol 1997 Jun, Vol 37 (6), Pg 453-73, PMID: 0009208352. 7.) Luscombe, GP, Slater, NA, Lyons, MB, Wynne, RD, Scheinbaum, ML, and Buckett, WR "Effect on radiolabelled-monoamine uptake in vitro of plasma taken from healthy volunteers administered the antidepressant sibutramine HCl." Psychopharmacology (Berl) 1990, Vol 100 (3), Pg 345-9, PMID: 0002315431. 8.) Luscombe, GP, Hopcroft, RH, Thomas, PC, and Buckett, WR "The contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride." Neuropharmacology 1989 Feb, Vol 28 (2), Pg 129-34, PMID: 0002541365. 9.) Connacher, AA, Bennet, WM, and Jung, RT "Clinical studies with the beta-adrenoceptor agonist BRL 26830A." Am J Clin Nutr 1992 Jan, Vol 55 (1 Suppl), Pg 258S-261S, PMID: 0001345890. 10.) Bray, GA "Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis." J Nutr 1991 Aug, Vol 121 (8), Pg 1146-62, PMID: 0001861165. 11-NP.) Bray, GA "The MONA LISA hypothesis. Most Obesities known Are Low In Sympathetic Activity." in "Progress in obesity research." eds. Y. Oomura (1990) pp. 61-6. 12.) Rothwell, NJ and Stock, MJ "Effect of diet and fenfluramine on thermogenesis in the rat: possible involvement of serotonergic mechanisms." Int J Obes 1987, Vol 11 (4), Pg 319-24, PMID: 0003667065. 13.) Van Gaal, LF, Vansant, GA, Steijaert, MC, and De Leeuw, IH "Effects of dexfenfluramine on resting metabolic rate and thermogenesis in premenopausal obese women during therapeutic weight reduction." Metabolism 1995 Feb, Vol 44 (2 Suppl 2), Pg 42-5, PMID: 0007869937. 14-NP.) Arch, JRS; Piercy, V; Thurlby, PL; Wilson, C, and Wilson, S "Thermogenic and lipolytic drugs for the treatment of obesity: old ideas and new possibilities." in "Rec Adv in Obesity Res: V." (1986) pp. 300-11. |
|
|
|
|||
