Zel , N-methyl-N-(2-propinyl)-2-methyl-1-phenylethylamine (10.1.14), is synthesized by the alkylation of (–)methyamphetamine (184.108.40.206) using propargyl-bromide .
There are a few known interactions between Zel and other medications that may potentially cause issues.
As always, the best way to minimize your risk is to keep your doctor up-to-date about any ongoing medications you are taking.
Some of these potential interactions include:
- Other antidepressants like fluoxetine (Prozac, Sarafem), clomipramine, and selective serotonin reuptake inhibitors (SSRIs) in general
- MAO inhibitors (MAOIs) like linezolid or moclobemide
- Opioidsor opioid-like drugs such as tramadol, dextromethorphan, methadone, or propoxyphene
The major enzyme in the body that metabolized Zel is CYP2B6. Therefore caution is advised when patients are taking other medications metabolized by this enzyme .
One study reported that women using hormonal birth control had excess levels of Zel (10-20 times higher than normal) after treatment . For this reason, the study’s authors suggest that the doses of one or both of these medications should be reduced when taken together. As always, make sure your doctor knows about all your current medications so that he- or she can help you avoid these potential issues.
Interactions with non-medical drugs are also possible. For example, due to Zel’s effects on several major neurotransmitter systems, it should also never be combined with alcohol . If you are prescribed Zel, talk to your doctor about cutting back (or even completely stopping) alcohol consumption.
The occurrence of stupor, muscular rigidity, severe agitation, and elevated temperature has been reported in some patients receiving the combination of Zel and meperidine. Symptoms usually resolve over days when the combination is discontinued. This is typical of the interaction of meperidine and MAOIs. Other serious reactions (including severe agitation, hallucinations, and death) have been reported in patients receiving this combination (see CONTRAINDICATIONS). Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and ELDEPRYL (Zel hcl) and selective serotonin reuptake inhibitors and ELDEPRYL. (See WARNINGS for details.) One case of hypertensive crisis has been reported in a patient taking the recommended doses of Zel and a sympathomimetic medication (ephedrine).
ELDEPRYL (Zel hcl) is contraindicated in patients with a known hypersensitivity to this drug.
ELDEPRYL (Zel hcl) is contraindicated for use with meperidine (DEMEROL & other trade names). This contraindication is often extended to other opioids. (See DRUG INTERACTIONS.)
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Assessment of the carcinogenic potential of Zel in mice and rats is ongoing.
Zel did not induce mutations or chromosomal damage when tested in the bacterial mutation assay in Salmonella typhimurium and in an in vivo chromosomal aberration assay. While these studies provide some reassurance that Zel is not mutagenic or clastogenic, they are not definitive because of methodological limitations. No definitive in vitro chromosomal aberration or in vitro mammalian gene mutation assays have been performed.
The effect of Zel on fertility has not been adequately assessed.
Other Possible Effects of Zel
Due to its ability to affect many different important biological mechanisms, Zel may have a number of additional effects on brain and bodily health. However, keep in mind that all of the effects described below are still in a very early stage of research, and much more research will still be needed to fully confirm any of these effects in humans – so take the findings below with a healthy grain of salt!
While Zel has been approved for safety and efficacy when used as directed, like any other drug it still has its share of potential side-effects that it is important to be aware of.
Keep in mind that the best way to minimize your overall risk of experiencing side-effects is to use this medication only as directed by your doctor, and to keep him or her fully informed about any other medications you are taking, other health conditions, and other relevant factors that may impact your treatment.
Zel can protect cultured dopaminergic neurons against the toxicity of MPP + and, in animal models, can reduce dopaminergic cell loss in response to MPTP. 407–410 Zel also protects against apoptotic cell death induced by serum and growth factor withdrawal, 411, 412 possibly via an increased production of Bcl2. Zel, by virtue of its MAO-B activity, will reduce the turnover of dopamine and so reduce free radical generation. The production of reactive oxygen species and free radical–mediated damage to lipids and proteins have been implicated in PD pathogenesis. Thus, this property, together with the ability for Zel to protect against MPTP toxicity, led to the evaluation of this drug in the first clinical trial for neuroprotection in PD.
The results of the DATATOP and other studies using Zel and the TEMPO study investigating rasagiline were discussed earlier. There appeared to be some benefit for Zel, but interpretation is difficult in view of trial design and the compound's inherent symptomatic action. The results of the delayed start design for TEMPO rasagiline were positive and support a neuroprotective action of the drug, but additional confirmatory trials are required before this drug can be accepted as neuroprotective.
Zel (l-desprenyl) is a methamphetamine derivative and a potent, irreversible, MAO-B selective inhibitor primarily used for the treatment of Parkinson’s disease.54,55
Indications and Usage for Zel
Zel capsules, USP are indicated as an adjunct in the management of Parkinsonian patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy. There is no evidence from controlled studies that Zel has any beneficial effect in the absence of concurrent levodopa therapy.
Evidence supporting this claim was obtained in randomized controlled clinical investigations that compared the effects of added Zel or placebo in patients receiving levodopa/carbidopa. Zel was significantly superior to placebo on all three principal outcome measures employed: change from baseline in daily levodopa/carbidopa dose, the amount of ‘off’ time, and patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (e.g., measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability and improved overall disability as assessed by walking and comparison to previous state).
Before taking Zel
Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking Zel it is important that your doctor or pharmacist knows:
- If you are pregnant or breast-feeding.
- If you have a stomach or duodenal ulcer.
- If you have high blood pressure, an irregular heartbeat, or angina pain.
- If you have had a mental health problem (in particular, psychosis).
- If you have a problem with the way your liver works, or with the way your k >
Zel is contraindicated in patients with a known hypersensitivity to this drug.
Zel is contraindicated for use with meper >Drug Interactions . )
Zel S >
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- a light-headed feeling, like you might pass out;
- trouble breathing;
- confusion, hallucinations, unusual thoughts or behavior;
- increased tremors or uncontrolled muscle movements;
- worsening side effects of your other medications;
- high levels of serotonin in the body (when taken with an antidepressant)--agitation, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting; or
- dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nausea, vomiting, severe chest pain, shortness of breath, pounding heartbeats, or seizure (convulsions).
You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.
Common side effects may include:
- nausea, stomach pain, constipation;
- skin rash or other irritation;
- sleep problems (insomnia); or
- mouth sores or ulcers, pain with swallowing (while using Zel orally disintegrating tablets).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Zel is a methamphetamine derivative and a potent, irreversible, MAO-B selective inhibitor primarily used for the treatment of Parkinson disease. 53,54 Because it is often cons >l -amphetamine (20% to 60% in urine) and l -methamphetamine (9% to 30% in urine). 53
In the canine model of narcolepsy, Zel (2mg/kg given orally) was demonstrated to be an effective anticataplectic agent, but this effect was found to be mediated by its amphetamine metabolites rather than MAO-B inhibition. 55 Several trials in human narcolepsy have demonstrated a good therapeutic efficacy of Zel in both sleepiness and cataplexy with relatively few side effects. 56,57 Zel 10 mg daily has no effect on the symptoms of narcolepsy, but 20 to 30 mg improves alertness and mood and reduces cataplexy, showing an effect comparable to d -amphetamine at the same dose. Zel may be an interesting alternative to the use of more classic stimulants because its potential for abuse has been reported to be very low.
8) Zel and Stroke Recovery
According to one double-blind randomized control trial in 24 stroke patients, Zel was reported to have shortened recovery times .
Similarly, in one animal study, Zel was reported to increase resistance to stroke, and even possibly reduce brain damage after stroke in mice .
However, if this effect is real, the mechanisms still haven’t been figured out – so a lot more research will still be needed.
Rationale for the Use of a Selective Monoamine Oxidase Type B Inhibitor in Parkinson's Disease
Many of the prominent symptoms of Parkinson's disease are due to a deficiency of striatal dopamine that is the consequence of a progressive degeneration and loss of a population of dopaminergic neurons which originate in the substantia nigra of the midbrain and project to the basal ganglia or striatum. Early in the course of Parkinson's Disease, the deficit in the capacity of these neurons to synthesize dopamine can be overcome by administration of exogenous levodopa, usually given in combination with a peripheral decarboxylase inhibitor (carbidopa).
With the passage of time, due to the progression of the disease and/or the effect of sustained treatment, the efficacy and quality of the therapeutic response to levodopa diminishes. Thus, after several years of levodopa treatment, the response, for a given dose of levodopa, is shorter, has less predictable onset and offset (i.e., there is 'wearing off'), and is often accompanied by side effects (e.g., dyskinesia, akinesias, on-off phenomena, freezing, etc.).
This deteriorating response is currently interpreted as a manifestation of the inability of the ever decreasing population of intact nigrostriatal neurons to synthesize and release adequate amounts of dopamine.
MAO B inhibition may be useful in this setting because, by blocking the catabolism of dopamine, it would increase the net amount of dopamine available (i.e., it would increase the pool of dopamine). Whether or not this mechanism or an alternative one actually accounts for the observed beneficial effects of adjunctive Zel is unknown.
Zel's benefit in Parkinson's disease has only been documented as an adjunct to levodopa/carbidopa. Whether or not it might be effective as a sole treatment is unknown, but past attempts to treat Parkinson's disease with non-selective MAOI monotherapy are reported to have been unsuccessful. It is important to note that attempts to treat Parkinsonian patients with combinations of levodopa and currently marketed non-selective MAO inhibitors were abandoned because of multiple side effects including hypertension, increase in involuntary movement, and toxic delirium.