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The Structure and Activity of Selegiline, its Figure 1: Selegiline (l-deprenyl), N-propargyl levo-methamphetamine Organic chemistry is for people who like to cook! Selegiline, or l-deprenyl, was first synthesized in 1962 by Joseph Knoll. It is a very close derivative of l-methamphetamine identical but for the addition of a propargyl group to its single nitrogen atom. l-Methamphetamine is itself one of the many derivatives of phenethylamine the foundation for a great number of com- pounds of psychopharmacological interest While selegiline does inherit some of the pharmacological actions characteristic of phenethylamines, the addition of the rather innocuous-looking propargylamine group compounds and complements those with its own, truly surprising, dimension of activity.
Pharmacological Activity of Propargylamines
The monoamine oxidase enzymes, types A and B, are the body’s primary means of deactivating amines, or compounds derived from ammonia by replacing one or more of its hydrogen atoms with hydrocarbon groups. Though both enzymes catalyse the oxidation reaction with amines resulting in the production of ammo- nia and hydrogen peroxide shown in equation they may be characterized by the compounds (or “substrates”) they work on, as well as by the compounds which inhibit their activity. While MAO-A preferentially deaminates serotonin and nora- drenaline and is selectively inhibited by clorgyline, MAO-B tends to catalyse the reduction of dopamine and β-phenethylamine and may be inhibited by aliphatic RCH2NH2 + H2O + O2 −→ RCHO + NH3 + H2O2 As a selective and irreversible inhibitor of MAO-B, selegiline prevents the deamination of dopamine and β-phenethylamine, thus increasing the concentra- tion of those monoamines while restricting the production of hydrogen peroxide, a pro-oxidant or “reactive oxygen species” (ROS). By increasing dopamine lev- els, selegiline forestalls and decreases by 30–40% the need for levodopa therapy in cases of Parkinson’s Disease, a condition marked by severe dopamine deficiencies.
The increase in phenethylamine caused by selegiline may also contribute to its ther- apeutic value for Parkinson’s, as it is known to promote the release of dopamine and inhibit its transport. Although most valuable as an adjunct to levodopa therapy, selegiline is somewhat effective as a monotherapy, improving scores on the Unified Parkinson’s Disease Rating Scale by 5–30%.
The “Free Radical Theory of Aging” hypothesizes that the rate at which one ages is proportional to the ratio of pro- to anti-oxidants. When the balance is tipped towards pro-oxidants, ROS are more free to cause oxidative damage, hastening the aging process. Selegiline is thought to tip the balance in the other direction in part, at least, by inhibiting the metabolism of monoamines by MAO-B and thereby diminishing the production of hydrogen peroxide. This action may seem even more significant in light of reports that MAO-B levels begin increasing with age around 50–60, is more active in Alzheimer’s and Parkinson’s patients, and is found in high Selegiline has, additionally, been demonstrated to protect against the oxidative damage to serotonin terminals caused by large doses (40 mg/kg) of MDMA This could be explained by selegiline’s inhibition of MAO-B: by interfering with the deamination of the large amount of dopamine released by MDMA, it would also inhibit the production of the ROS thought to cause the damage It seems just as likely, however, that this damage could be prevented by the antioxidant The propargyl group also appear to protect against neurodegeneration by pre- venting apoptosis, or programmed cell death. Marumaya et al have proposed that selegiline and related compounds bond to a protein with a tertiary structure very Figure 6: Rasagiline, N-propargyl-1-(R)aminoindan similar to that of MAO-B, triggering “the cellular process to repress the apoptotic Superoxide dismutase (SOD) and catalase are antioxidant enzymes (AOEs) which work to prevent oxidative damage to the body and brain by reactive oxygen species (ROS). Though Knoll initially found that selegiline increased the activity of AOEs, his subsequent research with a different strain of rat failed to corroborate this result. Further work by Kitani et al has done much to elucidate the relationship of selegiline to AOEs, concluding that the dose-effect graph follows an inverse U shape, increasing to a certain, optimal dose and declining steadily thereafter As an aside, the response of AOEs to selegiline is paralleled by that of the lifespan of various animals (mice, rats, hamsters, and beagles) to the same. Both dose-effect graphs follow an inverted U shape, and Kitani et al maintain this as the primary support for their working hypothesis that the upregulation of AOEs and extension of lifespan observed with selegiline treatment are causally connected.
This optimal dose is heaviliy dependent on the activity of the hepatic microso- mal cytochrome P-450 enzyme responsible for the metabolism of selegiline, which itself is dependent not only on the age, sex, and genetic strain of the organism, but also on the length of time over which selegiline is administered. The difficulty of extrapolating these results to humans is illustrated by studies in which Kitani ad- ministered various doses of selegiline to our closer relatives, beagles and monkeys: while a dose of 0.17 mg/kg, “roughly” equivalent to that prescribed for Parkinson’s Disease (10 mg/day), was most effective for young male monkeys, a much larger dose of 1.0 mg/kg gave the best results for female beagles.
Other propargylamines share in selegiline’s effect on AOEs, albeit with vary- ing degrees of potency. Of those listed by Kitani et al, selegiline is the most ef- fective, followed by rasagiline R-2HMP and R-2HP. Though the relation of the larger structures of these molecules to their effects on SOD and catalase is largely unknown, Kitani does expect that selegiline should be more potent than desmethylselegiline, given that R-2HMP is more potent than its desmethyl deriva- Catecholamine Activity Enhancement
Like many derivatives of phenethylamine, selegiline stimulates the activity of the sympathetic system of the brain. As a catecholamine activity enhancer (CAE), selegiline intensifies the response of catecholaminergic neurons by increasing the impulse-mediated release of catecholamines. It is unique, however, in that it does not displace catecholamines from their stores, which property tends to lead to de- pendence, as exemplified by dextro-methamphetamine In a fascinating article entitled “Sex, Performance, and Longevity,” Knoll es- tablishes an apparently solid, heretofore unknown, link between sexual activity, learning ability, and lifespan in rats via “a hitherto unknown brain mechanism that controls general activity and thereby, indirectly, the duration of life.” Knoll first shows that the lifespan of normal, placebo treated rats is proportional to their sexual activity and learning performance: rats predetermined to have “low” sexual and learning performance as measured by standard tests lived about 134 weeks, while those which scored as “high” performers lived about 151 weeks, or Finally, he reports that maintaining rats with a daily, 0.25 mg/kg dose of se- legiline until death lengthened lifespan and increased scores in tests of sexual and learning performance: selegiline-treated, low-performing rats lived about 152 weeks, or 13% longer than their untreated peers, and selegiline-treated, high-performing rats lived about 185 weeks, or 22% longer.
At each step, increases in lifespan are linked with increases in sexual perfor- mance, and each of these is tied to learning ability. Moreover, life-long mainte- nance of rats on selegiline is shown to increase all three as compared to placebo- treated peers; initially low-performing rats treated with selegiline outlive their un- treated, high-performing peers by roughly a month, improve in measures of sexual and learning performance, and maintain their ability to perform beyond that of their Pharmacokinetics
Selegiline is administered therapeutically at a dose of 5-10 mg. It is taken up by the body quickly, and reaches its peak concentration in the plasma within 30– 120 minutes. MAO-B is irreversibly inhibited by 90% within 30–90 minutes, and remains so until it can be re-synthesized by the body – a period of up to 40 days.
Selegiline is primarily metabolized in the liver by the cytochrome P450 en- zyme into desmethylselegiline l-methamphetamine and l-amphetamine These compounds are further metabolized by ring hydroxylation into p-hydroxy- amphetamine p-hydroxymethamphetamine, and p-hydroxy-N-propargylam- phetamine, or by β-carbon hydroxylation into ephedrine norephedrine, pseudo- Though selegiline is typically taken orally, transdermal administration may, in some ways, be favorable. When first-pass metabolism in the liver is circumvented, the maximum plasma concentration of selegiline is increased 60-fold, and the bal- ance of metabolites is altered significantly, halving the production of (levo) am- phetamines while increasing levels of desmethylselegiline, which is itself a propar- Figure 7: Nordeprenyl, Desmethylselegiline Composed primarily of a phenethylamine base and a propargylamine group, selegiline inherits characteristics of both. From phenethylamine, selegiline de- rives its ability to enhance catecholamine activity, multiplying the response of cat- echolaminergic nerves. From propargylamine, selegiline inherits its ability to in- hibit monoamine oxidase B, prevent apoptosis, protect against oxidative damage caused by the deamination of monoamines, and increase the activity of antioxidant Figure 12: MDMA (Ecstasy), 3,4-methylenedioxymethamphetamine Figure 13: Dopamine, 3,4-dihydroxyphenylethylamine Figure 16: MDPL, 3,4-methylenedioxy-N-propargylamphetamine Figure 17: Synthesis of l-deprenyl from phenylalanine enzymes. With the combination of these groups, selegiline exhibits more novel properties, including CAE without catecholamine release, and offers a unique and unlikely combination of mechanisms which work to make it a valuable treatment for Parkinson’s Disease. Last, but not least, is evidence that it can actually extend lifespan and preserve sexual and learning performance.
References
[1] M. D. Berry and A. A. Boulton. Aliphatic propargylamines as symptomatic and neuroprotective treatments for neurodegenerative diseases. Neurotoxicol-ogy and Teratology, 2002. In Press, Uncorrected Proof. Available online 10April 2002.
[2] CP de la Cruz, E Revilla, et al.
insulin-like growth factor-i (igf-i) levels in aged rats to young rat level.
Eur J Pharmacol, 327(3-2):215–20, May 1997. Abstract [Online]. [3] HC Dringenberg, PP Laporte, and P Diavolitsis.
of tacrine by deprenyl co-treatment in rats: Eeg and behavioral evidence.
Neuroreport, 11(16):3513–6, Nov 2000. Abstract [Online]. [4] David A. Durden, Lillian E. Dyck, Bruce A. Davis, Ya-Dong Liu, and Alan A. Boulton. Metabolism and pharmacokinetics, in the rat, of (R)-N-(2-heptyl)methylpropargylamine (R-2HMP), a new potent monoamine oxi-dase inhibitor and antiapoptotic agent. Drug Metabolism and Disposition,28(2):147–154, 2000.
[5] P. Foley, M. Gerlach, M.B.H. Youdim, and P. Riederer. MAO-B inhibitors: multiple roles in the therapy of neurodegenerative disorders? Parkinsonism& Related Disorders, 6:25–47, 2000.
[6] Steven Wm. Fowkes. Affidavit of testimony in Kimball case. [Online]. [7] Hasegawa, Matsubara, et al. Stereoselective analyses of selegiline metabo- lites: possible urinary markers for selegiline therapy.
101(2):95–106, April 1999. Abstract [Online]. [8] EH Heinonen, MI Anttila, HL Karnani, et al. Desmethylselegiline, a metabo- lite of selegiline, is an irreversible inhibitor of monoamine oxidase type Bin humans. J Clin Pharmacol, 37(7):602–9, July 1997. Abstract [Online].
[9] KENICHI KITANI, CHIYOKO MINAMI, TAKAKO YAMAMOTO, SET- SUKO KANAI, GWEN O. IVY, and MARIA-CRISTINA CARRILLO. Phar-macological interventions in aging and age-associated disorders: Potentials of propargylamines for human use. Annals of the New York Academy of Sci-ences, 959:295–307, 2002.
[10] J Knoll. Rationale for (-)-deprenyl (selegiline) medication in Parkinson’s disease and in prevention of age-related nigral changes. Biomed & Pharma-cother, 49:187–195, 1995.
(-)deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain. Pharmacol Toxicol, 82(2):57–66, Feb1998. Abstract [Online]. [13] J Knoll and I Miklya. Enhanced catecholaminergic and serotoninergic activ- ity in rat brain from weaning to sexual maturity: Rationale for prophylactic(-)deprenyl (selegiline) mediciation. Life Sciences, 56(8):611–620, 1995.
[14] J Knoll, I Miklya, B Knoll, R Marko, and K Kelemen. (-)deprenyl and (-)1- phenyl-2-propargylaminopentane, [(-) PPAP], act primarily as potent stimu-lants of action potential - transmitter release coupling in the catecholaminer-gic neurons. Life Sciences, 58(10):817–827, 1996.
[15] Wakoko Marumaya and Makoto Naoi. Neuroprotection by (-)-deprenyl and related compounds. Mechanisms of Ageing and Development, 111:189–200,1999.
[16] Takahiro Oka, Takuyo Yasusa, Takashi Ando, et al.
tive synthesis and absolute configuration of (-)-1-(benzofuran-2-yl)-2-propylaminopentane, ((-)-BPAP), a highly potent and selective catecholamin-ergic activity enhancer. Bioorganic and Medicinal Chemistry, 9:1213–1219,2001. [Online]. [17] ProfessorQ@selegiline.com. Selegiline (l-deprenyl): Synthesis. [Online].
[18] Seiichiro Shimazu, Kazue Takahata, et al.
propylaminopentane enhances locomotor activity in rats due to its ability toinduce dopamine release. European Journal of Pharmacology, 421:181–189,2001.
[19] Alexander Shulgin and Ann Shulgin.
l-deprenyl protects against 3,4-methylenedioxymethamphetamine-inducedlipid peroxidation and long-term serotonergic deficits.
Ther, 273(2):667–73, May 1995. Abstract [Online]. [22] T Thomas. Monoamine oxidase-B inhibitors in the treatment of Alzheimer’s disease. Neurobiol Aging, 21(2):348–8, March–April 2000. Abstract [On-line]. [23] T Thomas, C McLendon, and G Thomas. L-deprenyl: nitric oxide production and dilation of cerebral blood vessels. Neuroreport, 9(11):2595–600, August1998. Abstract [Online]. [24] S. ThyagaRajan, K.S. Madden, S.Y. Stevens, and D.L. Felten. Anti-tumor effect of l-deprenyl is associated with enhanced central and peripheral neu-rotransmission and immune reactivity in rats with carcinogen-induced mam-mary tumors. Journal of Neuroimmunology, 109:95–104, 2000.
[25] M.B.H. Youdim and K.F. Tipton. Rat striatal monoamine oxidase-B inhi- bition by l-deprenyl and rasagiline: its relationship to 2-phenylethylamine-induced stereotypy and Parkinson’s disease. Parkonsinism & Related Disor-ders, 8:247–253, 2002.

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