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Prakt [2002] - Various - Kreutzermusik

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Apomorphine brand names ApokynIxenseSpontaneUprima is a type of aporphine having activity as a non- selective dopamine agonist which activates both D 2 -like and, to a much lesser extent, D 1 -like receptors.

The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the - morphine suffix. Contrary to its name, apomorphine does not actually Prakt [2002] - Various - Kreutzermusik morphine or its skeleton, nor does it bind to opioid receptors.

The apo - prefix relates to it being a morphine derivative "[comes] from morphine". Historically, apomorphine has been tried for a variety of uses, including as a way to relieve anxiety and craving in alcoholics, an emetic to induce vomitingfor treating stereotypies repeated behaviour in farmyard animals, and more recently in treating erectile dysfunction.

Currently, apomorphine is used in the treatment of Parkinson's disease. It The System - infO Gates - Everybody Knows Everything a potent emetic and should not be administered without an antiemetic such as domperidone.

The emetic properties of apomorphine are exploited in veterinary medicine to induce therapeutic emesis in canines that have recently ingested toxic or foreign substances.

Apomorphine was Prakt [2002] - Various - Kreutzermusik used as a private treatment of heroin addictiona purpose for which it was championed by the author William S. Burroughs and others claimed that it was a "metabolic regulator" with a restorative dimension to a damaged or dysfunctional dopaminergic system.

There is more than enough anecdotal evidence to suggest that this offers a plausible route to an abstinence-based model; however, no clinical trials have ever tested this hypothesis. A recent study indicates that apomorphine might be a suitable marker for assessing central dopamine system alterations associated with chronic heroin consumption.

Apomorphine is used in advanced Parkinson's disease intermittent hypomobility "off" episodeswhere a decreased response to an anti-Parkinson drug such as L -DOPA causes muscle stiffness and loss of muscle control. It is used an average of three times a day. The main and absolute contraindication to using apomorphine is the concurrent use of adrenergic receptor antagonists; combined, they cause a severe drop in blood pressure and fainting. IV administration of apomorphine is highly discouraged, as it can crystallize in the veins and create a blood clot thrombus and block a pulmonary artery pulmonary embolism.

Nausea and vomiting are common side effects when first beginning therapy with apomorphine; [9] antiemetics such as trimethobenzamide or domperidone, dopamine antagonists, [10] are often used while first starting apomorphine. Other side effects include orthostatic hypotension and resultant fainting, sleepinessdizzinessrunny nosesweatingpalenessand flushing.

More serious side effects include dyskinesias especially when taking L -DOPAfluid accumulation in the limbs edemasuddenly falling asleep, confusion and hallucinationsincreased heart rate and heart palpitationsand persistent erections priaprism.

This side effect has The Man Goes On - Various - International P.E.A.C.E. Benefit Compilation exploited in studies attempting to treat erectile dysfunction. Apomorphine's R-enantiomer is an agonist of both D 1 and D 2 dopamine receptorswith higher activity at D 2.

The D 4 receptor in particular is an important target in the signaling pathway, and is connected to several neurological disorders.

Apomorphine improves motor function by activating dopamine receptors in the nigrostriatal pathwaythe limbic systemthe hypothalamusand the pituitary gland. Apomorphine also reduces the breakdown of dopamine in the brain though it inhibits its synthesis as well.

Apomorphine causes vomiting by acting on dopamine receptors in the chemoreceptor trigger zone of the medulla ; this activates the nearby vomiting center. Ten to twenty minutes after that, it reaches its peak concentration in the cerebrospinal fluid. Its lipophilic structure allows it to cross the blood—brain barrier.

Apomorphine possesses affinity for the following receptors note that a higher K i indicates a lower affinity : [25] [26] [27]. The half-life is 30—60 minutes, and the effects of the injection last for up to Василий Луканин - Various minutes. Apomorphine has a catechol structure similar to that of dopamine. Several techniques exist for the creation of apomorphine from morphine. More recent techniques create the apomorphine in a similar fashion, by heating it in the presence of any acid that will promote the essential dehydration rearrangement of morphine-type alkaloidssuch as phosphoric acid.

The method then deviates by including a water scavenger, which is essential to remove the water produced by the reaction that can react with the product and lead to decreased yield. The scavenger can be any reagent that will irreversibly react with water such as phthalic anhydride or titanium chloride.

The temperature required for the reaction varies based upon choice of acid and water scavenger. The pharmacological effects of the naturally-occurring analog aporphine in the blue lotus N. It is also observed in Egyptian erotic cartoons, suggesting that they were aware of its erectogenic properties.

The modern medical history of apomorphine begins with its synthesis by Arppe in [34] from morphine and sulfuric acidalthough it was named sulphomorphide at first. Matthiesen and Wright used hydrochloric acid instead of sulfuric acid in the process, naming the resulting compound apomorphine.

Initial interest in the compound was as an emetic, tested and confirmed safe by London doctor Samuel Gee[35] and for the treatment of stereotypies in farmyard animals. Apomorphine was one of the earliest used pharmacotherapies for alcoholism. The Keeley Cure s to contained apomorphine, among other ingredients, but the first medical reports of its use for more than pure emesis come from James Tompkins [37] and Charles Douglas. In four minutes free emesis followed, rigidity gave way to relaxation, excitement to somnolence, and without Prakt [2002] - Various - Kreutzermusik medication Prakt [2002] - Various - Kreutzermusik patient, who before had been wild and delirious, went off into a quiet sleep.

Accordingly it may be necessary to repeat the dose, and even to continue to give it twice or three times a day. Such repeated doses, however, do not require to be so large: 4 or even 3m is usually sufficient. This method was not limited to Douglas; the Irish doctor Francis Hare, who worked in a sanatorium outside London from onwards, also used low-dose apomorphine as a treatment, describing it as "the most useful single drug in the therapeutics of inebriety".

In the sanatorium it is used in three Prakt [2002] - Various - Kreutzermusik sets of circumstances: 1 in maniacal or hysterical drunkenness: 2 during the paroxysm of dipsomania, in order to still the craving for alcohol; and 3 in essential insomnia of a special variety He may be sober: he is free from the time being from any craving from alcohol.

The craving may return, however, and then it is necessary to repeat the injection, it may be several times at intervals of a few hours. These succeeding injections should be quite small, 3 to 6 min.

Doses of this size are rarely emetic. There is little facial pallor, a sensation as of the commencement of sea-sickness, perhaps a slight malaise with a sudden subsidence of the craving for alcohol, followed by a light and short doze. He also noted there appeared to be a significant prejudice against the use of apomorphine, both from the associations of its name and doctors being reluctant to give hypodermic injections to alcoholics.

In the US, the Harrison Narcotics Tax Act made working with any morphine derivatives extremely hard, despite apomorphine itself not being an opiate. In the s the neurotransmitter dopamine was discovered in the brain by Kathleen Montaguand characterised as a neurotransmitter a year later by Arvid Carlssonfor which he would be awarded the Nobel Prize. Ernst then discovered in that apomorphine was a powerful stimulant of dopamine receptors.

A series of studies of non-emetic apomorphine in the treatment of alcoholism were Introduction Et Allegro (Ravel) - Fragment - Henriette Sourgen / Françoise Léandri - Noël Pour Les E, with mostly positive results.

The use of apomorphine to treat "the shakes" was first suggested by Weil in France in[48] although seemingly not pursued until A later study found that combining the drug with the antiemetic domperidone improved results significantly. Aversion Prakt [2002] - Various - Kreutzermusik in alcoholism had its roots in Russia in the early s, [53] with early papers by Pavlov, Galant and Sluchevsky and Friken, [54] and would remain a strain in the Soviet treatment of alcoholism well into the s.

In Prakt [2002] - Various - Kreutzermusik US a particularly notable devotee was Dr Voegtlin, [55] who attempted aversion therapy using apomorphine in the mid to late s. However, he found apomorphine less able to induce negative feelings in his subjects than the stronger and more unpleasant emetic emetine.

In the UK, however, the publication of J Y Dent's who later went on to treat Burroughs paper "Apomorphine in the treatment of Anxiety States" [56] laid out the main method by which apomorphine would be used to treat alcoholism in Britain. His method in that paper is clearly influenced by the then-novel idea of aversion:. He is given his favourite drink, and his favourite brand of that drink He takes it stronger than is usual to him The small dose of apomorphine, one-twentieth of a grain [3.

A glass of whisky and water and a bottle of whisky are left by his bedside. At six o'clock four hours later he is again visited and the same treatment is again administered The nurse is told in confidence that if he does not drink, one-fortieth [1. In the morning at about ten he is again given one or two glasses of whisky and water The next day he is allowed to eat what he likes, he may drink as much tea as he likes He will be strong enough to get up and two days later he leaves the home.

However, even in he was suspicious of the idea that the treatment was pure conditioned reflex — "though vomiting is one of the ways that apomorphine relives the patient, I do not believe it to be its main therapeutic effect. It is now twenty-five years since I began treating cases of anxiety and alcoholism with apomorphine, and I read my first paper before this Society fourteen years ago. Up till then I had thought, and, unfortunately, I said in my paper, that the virtue of the treatment lay in the conditioned reflex of aversion produced in the patient.

This statement is not even a half truth… I have been forced to the conclusion that apomorphine has some further action than the production of a vomit.

This led to his development of lower-dose and non-aversive methods, which would inspire a positive trial of his method in Switzerland by Dr Harry Feldmann [57] and later scientific testing in the s, some time after his death.

However, the use of apomorphine in aversion therapy had escaped alcoholism, with its use to treat homosexuality leading to the death of a British Army Captain Billy Clegg HIll in[58] helping to cement its reputation as a dangerous drug used primarily in archaic behavioural therapies.

Burroughs wrote that apomorphine treatment was the only effective cure to opioid addiction he has encountered:. The apomorphine cure is qualitatively different from other methods of cure. I have tried them all. Short reduction, slow reduction, cortisoneantihistaminestranquilizerssleeping cures, tolserol, reserpine. None of these cures lasted beyond the first opportunity to relapse. I can say that I was never metabolically cured until I took the apomorphine cure The doctor, John Yerbury Dent, explained to me that apomorphine acts on the back brain to regulate the metabolism and normalize the blood stream in such a way that the enzyme stream of addiction is destroyed over a period of four to five days.

Once the back brain is regulated apomorphine can be discontinued and only used in case of relapse. He goes on to lament S[E]x - Various - Astúries fact that as of his writing, little to no research has been done on apomorphine or variations of the drug to study its effects on curing addiction, and perhaps the possibility of retaining the positive effects while removing the side effect of vomiting.

Despite his Prakt [2002] - Various - Kreutzermusik throughout his life, Burroughs never really cured his addiction and was back to using opiates within years of his apomorphine "cure". There is renewed interest in the use of apomorphine to treat addiction, in both smoking cessation [60] and alcoholism.

Apomorphine has been researched as a possible treatment for erectile dysfunction and female hypoactive sexual desire disorder, though the arousal effects were found not to be reliable enough.

One large study found that only InPrakt [2002] - Various - Kreutzermusik withdrew its new drug application Prakt [2002] - Various - Kreutzermusik an FDA review panel raised questions about the drug's safety, due to many clinical trial subjects fainting after taking the drug.

Once this functional group was altered, the inhibitory effect could be seen to decrease, reducing either the indirect or direct interference of the fibril formation. The protective effects of apomorphine were tested in mouse models with mutations in genes related to AD, such as the amyloid precursor protein gene.

Apomorphine was seen to significantly improve memory function through the Prakt [2002] - Various - Kreutzermusik successful completion of the Morris Water Maze.

The levels of the aberrant proteins that lead to neuronal disruption were also tested in the brains of mice. This result is consistent with the finding that another protein linked Bruises - Gene Loves Jezebel - Voodoo Dollies: The Best Of Gene Loves Jezebel AD, tau proteinwas seen to decrease with apomorphine treatment.

Apomorphine is used to inducing vomiting in dogs Prakt [2002] - Various - Kreutzermusik ingestion of various toxins or foreign bodies.


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  3. Apomorphine (brand names Apokyn, Ixense, Spontane, Uprima) is a type of aporphine having activity as a non-selective dopamine agonist which activates both D 2-like and, to a much lesser extent, D 1-like receptors. It also acts as an antagonist of 5-HT 2 and α-adrenergic receptors with high ishndoraakirtaum.infoinfolism: Hepatic, phase II.
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