Rasagiline Levodopa

Neither selegiline nor rasagiline should be taken by patients receiving meperidine. They should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the theoretical risk of acute toxic interactions of the serotonin syndrome type (see Chapter 16), but this is rarely encountered in practice. The adverse effects of levodopa may be increased by these drugs. 

In patients with severe parkinsonism and long-term complications of levodopa therapy such as the on-off phenomenon, a trial of treatment with a COMT inhibitor or rasagiline may be helpful. Regulation of dietary protein intake may also improve response fluctuations. Deep brain stimulation is often helpful in patients who fail to respond adequately to these measures. Treating patients who are young or have mild parkinsonism with rasagiline may delay disease progression and merits consideration. 

Rasagiline Inhibits MAO-B selectively, higher doses also inhibit MAO-A Increases dopamine stores in neurons may have neuroprotective effects Parkinson s disease adjunctive to levodopa smooths levodopa response Oral Toxicity interactions may cause serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic antidepressants... 

Selegiline Like rasagiline, adjunctive use with levodopa, parkinsonism may be less potent than rasagiline in MPTP-induced ... 

Monoamine-oxidase B inhibitors, such as selegiline and rasagiline, have a use alone in the management of early disease. Early treatment with selegiline alone has been shown to delay the need for levodopa therapy for some months, but other more effective drugs are preferred. Both dmgs can be used in conjunction with levodopa preparations to reduce end-of-dose deterioration in advanced disease. 

Monoamine oxidase type B inhibitors (rasagiline, selegiline) reduce the metabolism of dopamine by MAO-B. They are useful to delay disease progression in the early stages of the disease and as an adjunct to levodopa. 

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

Antiparkinsonian agents Bromocriptine Dopamine Entacapone Levodopa Peroxide Pramipexole Rasagiline derivatives Lasdostigil m30... 

Rabey JM, Sagi I, Huberman M, et al. Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson s disease A double-blind study as adjunctive therapy to levodopa. Clin Neuropharmacol 2000 23 324-330. 

FIGURE 20-7 Pharmacological preservation of L-DOPA and striatal dopamine. The principal site of action of inhibitors of catechol-O-methyltransferase (COMT) (such as tolcapone and entacapone) is in the peripheral circulation. They block the O-methylation of levodopa (l-DOPA) and increase the fraction of the drug available for delivery to the brain. Tolcapone also has effects in the CNS. Inhibitors of MAO-B, such as low-dose selegiline and rasagiline, will act within the CNS to reduce oxidative deamination of DA, thereby enhancing vesicular stores. AAD, aromatic L-amino acid decarboxylase DA, dopamine DOPAC, 3,4-dihydroxyphenylacetic acid MAO, monoamine oxidase 3MT, 3-methoxyl-tyramine 3-O-MD, 3-O-methyl DOPA. 

Selegiline and rasagiline are propargylamine-type selective inhibitors of MAO-B, which inactivates dopamine in the brain. The MAO-B inhibitors extend the duration of response to levodopa by reducing metabolism of dopamine thus, the dose of levodopa can be reduced without loss of therapeutic benefit (3). It has been proposed that MAO-B inhibitors may prevent formation of neurotoxic oxidation products of dopamine and slow neurodegeneration in Parkinson s disease however, data from recent clinical studies do not support this attractive neuroprotective hypothesis (54,55). Nevertheless, MAO-B inhibitors have a beneficial effect on motor fluctuations because of their levodopa-sparing effect (56). 

No serious interaction occurs between levodopa and selegiline, although the dose of levodopa may need to be reduced when selegiline is added. Levodopa does not affect rasagiline clearance. 

The manufacturer notes that levodopa had no effect on rasagiline clearance. ... 

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