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Fairlee, Here is some information about the new medications alleged to
be released this year for PD, including ropinirole. I hope this is
useful....Carole
>Up And Coming Medical Therapies for Parkinson's Disease
>
>by Matthias C. Kurth, MD, Ph.D., Medical Director and Advisor for
>Young Parkinsonians and the US NPR YOPPERS FORUM
>
> The coming year will bring new and exciting treatment
>options for Parkinson's disease patients. Four new drugs, all shown
>to improve patients' symptoms, are expected to be approved by the
>Federal Drug Administration (FDA). Each drug offers unique
>advantages that will greatly increase patient and physician choices
>in developing a therapeutic program to minimize the impact of
>Parkinson's disease throughout the day. These agents will be
>particularly useful for young onset patients since two of
>them may offer some element of neuroprotection and all four
>agents will enhance patients' well-being by improving symptom
>control. In preparation for the release of these agents, a review
>of their properties, mechanisms of action and results of clinical
>trials is in order. This knowledge will empower patients and
>physicians to combine the appropriate medications for optimal
>control of parkinsonian symptoms.
>
>Catechol-O-Methyl Transferase Inhibitors
>
> One new approach to treating Parkinson's disease involves
>prolonging the action of levodopa by inhibiting the enzyme catechol-
>o-methyltransferase (COMT) involved in the metabolism of levodopa
>and dopamine. inhibition of this enzyme in the body decreases the
>concentration of a levodopa metabolite, 3-0-methyldopa, which may
>have a role in inducing or aggravating levodopa response
>fluctuations. More importantly, blood levels of levodopa are
>maintained for a longer time and patients experience a smoother,
>more beneficial effect from each dose of levodopa.
>
>Tolcapone (Tasmar(r), Hoffman-LaRoche)
>
> Tolcapone is the most potent COMT inhibitor currently
>in clinical development. Studies in patients with Parkinson's
>disease in the United States and Europe are complete and have
>been submitted to the FDA. Tolcapone prolongs the effects of
>levodopa thereby decreasing motor response fluctuations in patients
>and improving quality of life. Patients on levodopa that do not
>experience motor fluctuations also benefited significantly through
>improved quality of life and decreased symptoms.
> Tolcapone is given three times daily in doses from 100 mg
>to 200 mg in addition to the patient's levodopa medication schedule.
>Peak effect of tolcapone is reached in about 1 - 2 hours and
>maintained for the duration of the 6 hour dosing interval.
>Patients experience better control of their Parkinsonian symptoms
>while needing lower doses of levodopa. Side effects are few, but
>include occasional mild headache, nausea, loose stools, change
>in urine color, and in some patients a transient increase in
>dyskinesia. Tolcapone is absorbed by the small intestine and
>metabolized by the liver. Food delays the absorption of tolcapone
>somewhat, but this does not appear to be clinically significant.
>The ability of this compound to prolong blood and brain levels of
>levodopa while reducing the levels of potentially toxic metabolites
>should be an important development in the treatment of
>Parkinson's disease.
>
>Entacapone (no brandname available. Orion/Farmos and Sandoz)
>
> Entacapone is another new catechol-o-methyltransferase
>inhibitor. Like tolcapone, this compound improves the effectiveness
>of levodopa by decreasing fluctuations in medication response
>through inhibition of COMT.
> Studies to determine long-term safety and benefits of
>entacapone as a supplement to levodopa treatment in Parkinson's
>disease patients with reduced benefits or complications from
>levodopa have been completed in the United States and Europe.
>Entacapone enhances the effects of levodopa and is safe. Occasional
>mild side effects include headache, dizziness. nausea, loose stools,
>increased dyskinesia and changes in the color of urine.
> Entacapone is taken with each dose of levodopa. Peak effect
>is within one hour and its duration of action closely matches that
>of carbidopa/levodopa. These properties suggest that a combination
>tablet containing levodopa, carbidopa and entacapone may be feasible
>and desirable. Current plans include further studies to determine the
>benefit of entacapone in patients taking levodopa, but not
>experiencing motor fluctuations.
>
> Both tolcapone and entacapone are potent COMT inhibitors
>that prolong the duration of levodopa activity in patients with
>Parkinson's disease. Differences in the side effect profile,
>dosing schedule and potency will need to be addressed in comparative
>studies. Both tolcapone and entacapone will be valuable adjuncts for
>all patients using levodopa therapy.
>
>New Dopamine Agonists
>
> As soon as levodopa became available for the treatment of
>Parkinson's disease, efforts to find medications that could mimic
>it's dramatic effect on the symptoms of Parkinson's disease, but
>with fewer side effects, were begun. The result of this search
>yielded the well known dopamine agonists bromocriptine (Parlodel(r))
>and pergolide (Permax(r)). Neither met the desired expectation of
>fully replacing levodopa. Only the nonspecific dopamine agonist,
>apomorphine, has the spectrum of efficacy needed to fully treat
>patients in a manner similar to levodopa. Unfortunately, apomorphine
>has significant side effects and is difficult to store and administer.
>In a significant step towards achieving true levodopa replacement,
>two new agents are currently under review by the FDA for use in
>patients with early Parkinson's disease. In addition to having
>sufficient potency to act as first line therapy, these two drugs
>may also have neuroprotective effects that slow disease progression.
>
>Pramipexole (Mirapex(r), Pharmacia & Upjohn
>
> Pramipexole is a potent, non-ergot dopamine agonist used
>alone in treating patients not yet taking levodopa and as an adjunct
>to levodopa in treating advanced Parkinson's disease patients. While
>stimulating the dopamine D2-receptor, pramipexole may be effective
>in either blocking or selectively not stimulating the D1-receptor,
>thereby preventing dyskinesia. More recently, a specific dopamine
>D3 receptor activity has been identified and linked to a
>neurotrophic effect. In tissue culture models of Parkinson's
>disease, pramipexole protected neurons from specific dopaminergic
>neurotoxins, while bromocriptine and pergolide had no such effect.
>Pramipexole may also delay the need for levodopa and the development of
>dyskinesla. End of dose wearing off is reduced in patients with more
>advanced disease receiving pramipexole and levodopa.
> Patients in the United States, Canada and Europe have been
>treated with pramipexole in doses ranging from 0.1 mg to 5 mg daily.
>No dose-limiting toxicity was identified. Tolerability and safety were
>excellent with only occasional dizziness, nausea, vomiting, insomnia
>or somnolence and visual hallucinations identified as primary side
>effects. Symptomatic low blood pressure was not a significant side
>effect. The half-life of pramipexole is about 9-12 hours, easily
>allowing a three times a day schedule. The drug is excreted by the
>kidneys so that patients with kidney problems may need to be
>monitored closely for side effects.
>
>Ropinirole (Requip(r), Smith, Kline and Beecham)
>
> Ropinirole is a potent, highly selective, dopamine agonist,
>not related to pramipexole or the ergot derived drugs, developed for
>early therapy in Parkinson's disease patients not yet treated with
>levodopa and as adjunct therapy in treating Parkinson's disease
>patients not optimally controlled on levodopa. This potent D2-dopamine
>agonist is active both centrally and peripherally with central
>nervous system and cardiovascular activity seen. Antidepressant and
>anxiolytic effects have also been noted in patients with
>Parkinson's disease. Evidence of a possible neuroprotective effect
>has been documented.
> More than 300 patients with Parkinson's disease have
>completed placebo-controlled studies of ropinirole, taking doses up
>to 10 mg daily. Typical dopamineric side effects such as nausea,
>vomiting and orthostatic hypotension may occur at doses above 0.5 mg.
>Incremental dosage increases minimize these side effects, and the drug
>is tolerated extremely well by the majority of patients. A three times
>daily dosing schedule of lower doses given with meals allows for fewer
>side effects and closer conformance to it's half-life of 3.5-5 hours.
>
>Cabergoline (no brandname available, Pharmacia & Upjohn)
>
> Cabergoline, an ergoline derivative related to bromocriptine
>and pergolide, is a D2-specific dopaminergic agonist that is more
>potent and longer-acting than other dopamine agonists currently used
>to treat Parkinson's disease. In patients receiving levodopa, it
>effectively decreases levodopa response fluctuations and allows for
>lower levodopa doses. Plasma activity peaks between 0.5 and 4 hours
>with a half-life of about 7.5 hours and a slower elimination of 68-72
>hours.
> Patients in Italy, the United States and Canada have been
>treated with cabergoline once daily in dosages from 0.5 to 5.0 mg.
>Side effects are typical for dopaminergic agents and can include
>dizziness, nausea, dry mouth and orthostatic hypotension. Episodes
>of visual hallucinations also occurred in a few patients. The once
>daily schedule and long-acting effects offer greater compliance and
>provide greater control of motor fluctuations than currently
>available dopamine agonists. Unfortunately, this drug may not be
>offered as an anti-parkinsonian agent, but instead may only be
>marketed as a prolactin suppressing agent to stop lactation. At this
>time, no efforts to market this drug for Parkinson's disease are
>underway.
>
> Two new dopamine agonists, chemically different than
>currently used agents, are under review at the FDA for possible use
>in the treatment of Parkinson's disease. Both agents have
>demonstrated benefit in improving symptoms in patients with early
>(untreated) and late (levodopa treated) Parkinson's disease.
>Differences in benefit profiles, side effects and metabolism
>of the drugs will allow patients to find the right medication for
>their particular needs. If the potential of neuroprotection is born
>out in future studies then these agents will truly be a major advance
>in the treatment of Parkinson's disease. A third drug that offered
>once a day dosing may never be released for Parkinson's disease
>despite evidence of efficacy and safety.
>
>
> The treatment options for patients diagnosed with
>Parkinson's disease will be increased significantly with the
>introduction of these new medications. Combining the right amount
>and frequency of each medication in an individual will be more
>complicated in some ways, yet simpler in other ways. One prediction
>would be that newly diagnosed patients will begin therapy with
>one of the new dopamine agonists. Later such patients might
>consider adding one of the older drugs that offers additional hope
>of neuroprotection, either amandatine or selegiline.
> Another prediction Is that patients already taking levodopa,
>either in the form of Sinemet(r) (primarily taken by US patients)
>or Madopar(r) (used mainly in Europe), would want to consider addition
>of a catechol-o-methyltransferase inhibitor, either tolcapone or
>entacapone. Significant improvements in symptom control and reduced
>wearing-off can be expected immediately. Both medications, work well
>with either regular carbidopa/levodopa and the slow-release
>formulation of Sinemet CR(r). Patients with a stable response to
>levodopa should experience improvement without needing significant
>adjustments in levodopa dosages. Some adjustments might be warranted
>in patients with significant levodopa induced dyskinesia or other
>dopaminergic side effects.
> The introduction of these new medications will make 1997 one
>of the most exciting years for advancements in the treatment of
>Parkinson's disease. Patients, family members, caregivers, physicians
>and health care systems all over the world will benefit, all because
>of the diligent application of our rapidly growing understanding of
>the functions of the human central nervous system. Given the pace of
>progress over the last few years, a true understanding of the cause
>and ultimate cure for Parkinson's disease should not be too far in
>the future.
>John Cottingham To search the Parkinsn archive, send search requests
> to [log in to unmask] with Archive Search as the subject.
>LibraryH Searches of the Subject: line, From: line and Body are
> possible. Look for "Revised Current Topics...." message
>HomeBoy for Articles and Studies available by e-mail.
> PARKINSONIANS WORLD-WIDE GIVE THANKS IN MEMORY OF ALAN
>[log in to unmask] BONANDER.....WHERE EVER YOU ARE!
>
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2004, Week 4 June 2004, Week 3 June 2004, Week 2 June 2004, Week 1 May 2004, Week 5 May 2004, Week 4 May 2004, Week 3 May 2004, Week 2 May 2004, Week 1 April 2004, Week 5 April 2004, Week 4 April 2004, Week 3 April 2004, Week 2 April 2004, Week 1 March 2004, Week 5 March 2004, Week 4 March 2004, Week 3 March 2004, Week 2 March 2004, Week 1 February 2004, Week 5 February 2004, Week 4 February 2004, Week 3 February 2004, Week 2 February 2004, Week 1 January 2004, Week 5 January 2004, Week 4 January 2004, Week 3 January 2004, Week 2 January 2004, Week 1 December 2003, Week 5 December 2003, Week 4 December 2003, Week 3 December 2003, Week 2 December 2003, Week 1 November 2003, Week 5 November 2003, Week 4 November 2003, Week 3 November 2003, Week 2 November 2003, Week 1 October 2003, Week 5 October 2003, Week 4 October 2003, Week 3 October 2003, Week 2 October 2003, Week 1 September 2003, Week 5 September 2003, Week 4 September 2003, Week 3 September 2003, Week 2 September 2003, Week 1 August 2003, Week 5 August 2003, Week 4 August 2003, Week 3 August 2003, Week 2 August 2003, Week 1 July 2003, Week 5 July 2003, Week 4 July 2003, Week 3 July 2003, Week 2 July 2003, Week 1 June 2003, Week 5 June 2003, Week 4 June 2003, Week 3 June 2003, Week 2 June 2003, Week 1 May 2003, Week 5 May 2003, Week 4 May 2003, Week 3 May 2003, Week 2 May 2003, Week 1 April 2003, Week 5 April 2003, Week 4 April 2003, Week 3 April 2003, Week 2 April 2003, Week 1 March 2003, Week 5 March 2003, Week 4 March 2003, Week 3 March 2003, Week 2 March 2003, Week 1 February 2003, Week 4 February 2003, Week 3 February 2003, Week 2 February 2003, Week 1 January 2003, Week 5 January 2003, Week 4 January 2003, Week 3 January 2003, Week 2 January 2003, Week 1 December 2002, Week 5 December 2002, Week 4 December 2002, Week 3 December 2002, Week 2 December 2002, Week 1 November 2002, Week 5 November 2002, Week 4 November 2002, Week 3 November 2002, Week 2 November 2002, Week 1 October 2002, Week 5 October 2002, Week 4 October 2002, Week 3 October 2002, Week 2 October 2002, Week 1 September 2002, Week 5 September 2002, Week 4 September 2002, Week 3 September 2002, Week 2 September 2002, Week 1 August 2002, Week 5 August 2002, Week 4 August 2002, Week 3 August 2002, Week 2 August 2002, Week 1 July 2002, Week 5 July 2002, Week 4 July 2002, Week 3 July 2002, Week 2 July 2002, Week 1 June 2002, Week 5 June 2002, Week 4 June 2002, Week 3 June 2002, Week 2 June 2002, Week 1 May 2002, Week 5 May 2002, Week 4 May 2002, Week 3 May 2002, Week 2 May 2002, Week 1 April 2002, Week 5 April 2002, Week 4 April 2002, Week 3 April 2002, Week 2 April 2002, Week 1 March 2002, Week 5 March 2002, Week 4 March 2002, Week 3 March 2002, Week 2 March 2002, Week 1 February 2002, Week 4 February 2002, Week 3 February 2002, Week 2 February 2002, Week 1 January 2002, Week 5 January 2002, Week 4 January 2002, Week 3 January 2002, Week 2 January 2002, Week 1 December 2001, Week 5 December 2001, Week 4 December 2001, Week 3 December 2001, Week 2 December 2001, Week 1 November 2001, Week 5 November 2001, Week 4 November 2001, Week 3 November 2001, Week 2 November 2001, Week 1 October 2001, Week 5 October 2001, Week 4 October 2001, Week 3 October 2001, Week 2 October 2001, Week 1 September 2001, Week 5 September 2001, Week 4 September 2001, Week 3 September 2001, Week 2 September 2001, Week 1 August 2001, Week 5 August 2001, Week 4 August 2001, Week 3 August 2001, Week 2 August 2001, Week 1 July 2001, Week 5 July 2001, Week 4 July 2001, Week 3 July 2001, Week 2 July 2001, Week 1 June 2001, Week 5 June 2001, Week 4 June 2001, Week 3 June 2001, Week 2 June 2001, Week 1 May 2001, Week 5 May 2001, Week 4 May 2001, Week 3 May 2001, Week 2 May 2001, Week 1 April 2001, Week 5 April 2001, Week 4 April 2001, Week 3 April 2001, Week 2 April 2001, Week 1 March 2001, Week 5 March 2001, Week 4 March 2001, Week 3 March 2001, Week 2 March 2001, Week 1 February 2001, Week 4 February 2001, Week 3 February 2001, Week 2 February 2001, Week 1 January 2001, Week 5 January 2001, Week 4 January 2001, Week 3 January 2001, Week 2 January 2001, Week 1 December 2000, Week 5 December 2000, Week 4 December 2000, Week 3 December 2000, Week 2 December 2000, Week 1 November 2000, Week 5 November 2000, Week 4 November 2000, Week 3 November 2000, Week 2 November 2000, Week 1 October 2000, Week 5 October 2000, Week 4 October 2000, Week 3 October 2000, Week 2 October 2000, Week 1 September 2000, Week 5 September 2000, Week 4 September 2000, Week 3 September 2000, Week 2 September 2000, Week 1 August 2000, Week 5 August 2000, Week 4 August 2000, Week 3 August 2000, Week 2 August 2000, Week 1 July 2000, Week 5 July 2000, Week 4 July 2000, Week 3 July 2000, Week 2 July 2000, Week 1 June 2000, Week 5 June 2000, Week 4 June 2000, Week 3 June 2000, Week 2 June 2000, Week 1 May 2000, Week 5 May 2000, Week 4 May 2000, Week 3 May 2000, Week 2 May 2000, Week 1 April 2000, Week 5 April 2000, Week 4 April 2000, Week 3 April 2000, Week 2 April 2000, Week 1 March 2000, Week 5 March 2000, Week 4 March 2000, Week 3 March 2000, Week 2 March 2000, Week 1 February 2000, Week 5 February 2000, Week 4 February 2000, Week 3 February 2000, Week 2 February 2000, Week 1 January 2000, Week 5 January 2000, Week 4 January 2000, Week 3 January 2000, Week 2 January 2000, Week 1 December 1999, Week 5 December 1999, Week 4 December 1999, Week 3 December 1999, Week 2 December 1999, Week 1 November 1999, Week 5 November 1999, Week 4 November 1999, Week 3 November 1999, Week 2 November 1999, Week 1 October 1999, Week 5 October 1999, Week 4 October 1999, Week 3 October 1999, Week 2 October 1999, Week 1 September 1999, Week 5 September 1999, Week 4 September 1999, Week 3 September 1999, Week 2 September 1999, Week 1 August 1999, Week 5 August 1999, Week 4 August 1999, Week 3 August 1999, Week 2 August 1999, Week 1 July 1999, Week 5 July 1999, Week 4 July 1999, Week 3 July 1999, Week 2 July 1999, Week 1 June 1999, Week 5 June 1999, Week 4 June 1999, Week 3 June 1999, Week 2 June 1999, Week 1 May 1999, Week 5 May 1999, Week 4 May 1999, Week 3 May 1999, Week 2 May 1999, Week 1 April 1999, Week 5 April 1999, Week 4 April 1999, Week 3 April 1999, Week 2 April 1999, Week 1 March 1999, Week 5 March 1999, Week 4 March 1999, Week 3 March 1999, Week 2 March 1999, Week 1 February 1999, Week 4 February 1999, Week 3 February 1999, Week 2 February 1999, Week 1 January 1999, Week 5 January 1999, Week 4 January 1999, Week 3 January 1999, Week 2 January 1999, Week 1 December 1998, Week 5 December 1998, Week 4 December 1998, Week 3 December 1998, Week 2 December 1998, Week 1 November 1998, Week 5 November 1998, Week 4 November 1998, Week 3 November 1998, Week 2 November 1998, Week 1 October 1998, Week 5 October 1998, Week 4 October 1998, Week 3 October 1998, Week 2 October 1998, Week 1 September 1998, Week 5 September 1998, Week 4 September 1998, Week 3 September 1998, Week 2 September 1998, Week 1 August 1998, Week 5 August 1998, Week 4 August 1998, Week 3 August 1998, Week 2 August 1998, Week 1 July 1998, Week 5 July 1998, Week 4 July 1998, Week 3 July 1998, Week 2 July 1998, Week 1 June 1998, Week 5 June 1998, Week 4 June 1998, Week 3 June 1998, Week 2 June 1998, Week 1 May 1998, Week 5 May 1998, Week 4 May 1998, Week 3 May 1998, Week 2 May 1998, Week 1 April 1998, Week 5 April 1998, Week 4 April 1998, Week 3 April 1998, Week 2 April 1998, Week 1 March 1998, Week 5 March 1998, Week 4 March 1998, Week 3 March 1998, Week 2 March 1998, Week 1 February 1998, Week 5 February 1998, Week 4 February 1998, Week 3 February 1998, Week 2 February 1998, Week 1 January 1998, Week 5 January 1998, Week 4 January 1998, Week 3 January 1998, Week 2 January 1998, Week 1 December 1997, Week 5 December 1997, Week 4 December 1997, Week 3 December 1997, Week 2 December 1997, Week 1 November 1997, Week 5 November 1997, Week 4 November 1997, Week 3 November 1997, Week 2 November 1997, Week 1 October 1997, Week 5 October 1997, Week 4 October 1997, Week 3 October 1997, Week 2 October 1997, Week 1 September 1997, Week 5 September 1997, Week 4 September 1997, Week 3 September 1997, Week 2 September 1997, Week 1 August 1997, Week 5 August 1997, Week 4 August 1997, Week 3 August 1997, Week 2 August 1997, Week 1 July 1997, Week 5 July 1997, Week 4 July 1997, Week 3 July 1997, Week 2 July 1997, Week 1 June 1997, Week 5 June 1997, Week 4 June 1997, Week 3 June 1997, Week 2 June 1997, Week 1 May 1997, Week 5 May 1997, Week 4 May 1997, Week 3 May 1997, Week 2 May 1997, Week 1 April 1997, Week 5 April 1997, Week 4 April 1997, Week 3 April 1997, Week 2 April 1997, Week 1 March 1997, Week 5 March 1997, Week 4 March 1997, Week 3 March 1997, Week 2 March 1997, Week 1 February 1997, Week 5 February 1997, Week 4 February 1997, Week 3 February 1997, Week 2 February 1997, Week 1 January 1997, Week 5 January 1997, Week 4 January 1997, Week 3 January 1997, Week 2 January 1997, Week 1 December 1996, Week 5 December 1996, Week 4 December 1996, Week 3 December 1996, Week 2 December 1996, Week 1 November 1996, Week 5 November 1996, Week 4 November 1996, Week 3 November 1996, Week 2 November 1996, Week 1 October 1996, Week 5 October 1996, Week 4 October 1996, Week 3 October 1996, Week 2 October 1996, Week 1 September 1996, Week 5 September 1996, Week 4 September 1996, Week 3 September 1996, Week 2 September 1996, Week 1 August 1996, Week 5 August 1996, Week 4 August 1996, Week 3 August 1996, Week 2 August 1996, Week 1 July 1996, Week 5 July 1996, Week 4 July 1996, Week 3 July 1996, Week 2 July 1996, Week 1 June 1996, Week 5 June 1996, Week 4 June 1996, Week 3 June 1996, Week 2 June 1996, Week 1 May 1996, Week 5 May 1996, Week 4 May 1996, Week 3 May 1996, Week 2 May 1996, Week 1 April 1996, Week 5 April 1996, Week 4 April 1996, Week 3 April 1996, Week 2 April 1996, Week 1 March 1996, Week 5 March 1996, Week 4 March 1996, Week 3 March 1996, Week 2 March 1996, Week 1 February 1996, Week 5 February 1996, Week 4 February 1996, Week 3 February 1996, Week 2 February 1996, Week 1 January 1996, Week 5 January 1996, Week 4 January 1996, Week 3 January 1996, Week 2 January 1996, Week 1 December 1995, Week 5 December 1995, Week 4 December 1995, Week 3 December 1995, Week 2 December 1995, Week 1 November 1995, Week 5 November 1995, Week 4 November 1995, Week 3 November 1995, Week 2 November 1995, Week 1 October 1995, Week 5 October 1995, Week 4 October 1995, Week 3 October 1995, Week 2 October 1995, Week 1 September 1995, Week 5 September 1995, Week 4 September 1995, Week 3 September 1995, Week 2 September 1995, Week 1 August 1995, Week 5 August 1995, Week 4 August 1995, Week 3 August 1995, Week 2 August 1995, Week 1 July 1995, Week 5 July 1995, Week 4 July 1995, Week 3 July 1995, Week 2 July 1995, Week 1 June 1995, Week 5 June 1995, Week 4 June 1995, Week 3 June 1995, Week 2 June 1995, Week 1 May 1995, Week 5 May 1995, Week 4 May 1995, Week 3 May 1995, Week 2 May 1995, Week 1 April 1995, Week 5 April 1995, Week 4 April 1995, Week 3 April 1995, Week 2 April 1995, Week 1 March 1995, Week 5 March 1995, Week 4 March 1995, Week 3 March 1995, Week 2 March 1995, Week 1 February 1995, Week 4 February 1995, Week 3 February 1995, Week 2 February 1995, Week 1 January 1995, Week 5 January 1995, Week 4 January 1995, Week 3 January 1995, Week 2 January 1995, Week 1 December 1994, Week 5 December 1994, Week 4 December 1994, Week 3 December 1994, Week 2 December 1994, Week 1 November 1994, Week 5 November 1994, Week 4 November 1994, Week 3 November 1994, Week 2 November 1994, Week 1 October 1994, Week 5 October 1994, Week 4 October 1994, Week 3 October 1994, Week 2 October 1994, Week 1 September 1994, Week 5 September 1994, Week 4 September 1994, Week 3 September 1994, Week 2 September 1994, Week 1 August 1994, Week 5 August 1994, Week 4 August 1994, Week 3 August 1994, Week 2 August 1994, Week 1 July 1994, Week 5 July 1994, Week 4 July 1994, Week 3 July 1994, Week 2 July 1994, Week 1 June 1994, Week 5 June 1994, Week 4 June 1994, Week 3 June 1994, Week 2 June 1994, Week 1 May 1994, Week 5 May 1994, Week 4 May 1994, Week 3 May 1994, Week 2 May 1994, Week 1 April 1994, Week 5 April 1994, Week 4 April 1994, Week 3 April 1994, Week 2 April 1994, Week 1 March 1994, Week 5 March 1994, Week 4 March 1994, Week 3 March 1994, Week 2 March 1994, Week 1 February 1994, Week 4 February 1994, Week 3 February 1994, Week 2 February 1994, Week 1 February 1994 January 1994 December 1993 November 1993
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