No pharmacokinetic information is available on Endopryl or its metabolites in renally impaired subjects.
Before taking Endopryl
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 Endopryl 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 >
Use During Pregnancy and Breastfeeding
Endopryl was classified as a category “C” risk drug during pregnancy under the old FDA risk classifications. The risks of Endopryl use during pregnancy have not been properly investigated. Therefore, make sure you let your doctor know if you are pregnant (or are planning on becoming pregnant while being treated with Endopryl).
It also is not yet known if Endopryl is found in breast milk, and caution is therefore generally advised during breastfeeding. In general, discontinuation is advised unless the therapy is absolutely necessary – but .
Endopryl and ADHD
Although Endopryl has not been officially FDA-approved for this purpose, it is not uncommon for doctors to prescribe this medication in order to help improve or control the symptoms of ADHD.
The main rationale for using Endopryl in this way stems from its potential to increase dopamine levels throughout the brain. One of dopamine’s many important functions is to promote attention and focus. Additionally, low levels of dopamine in certain specific parts of the brain are believed to be responsible for some of the attention problems frequently seen in ADHD .
Although the evidence for this use of Endopryl is not quite as strong as it is for Parkinson’s and depression, there is still considerable scientific support behind its use in ADHD. For example, in a double-blind randomized controlled trial in 11 children with ADHD, Endopryl was reported to improve sustained attention, learning, and peer interactions, while also reducing hyperactivity .
Similarly, in different two double-blind randomized controlled trials with 40 and 28 children each, this drug was reported to be as effective as methylphenidate (a central nervous system stimulant, commonly sold as Ritalin) in improving the symptoms of ADHD. Better yet, Endopryl was also reported to cause fewer side effects .
However, at least one study contradicts some of this evidence: in one study of 24 adults with ADHD, Endopryl was reported to be no more effective than placebo in improving ADHD symptoms .
Mechanism of Action
Endopryl primarily blocks the activity of MAO-B and – at higher doses – also MAO-A. These enzymes break down dopamine and other monoamine neurotransmitters (serotonin and noradrenaline). Thus, by blocking the activity of these enzymes, Endopryl increases the overall level of these neurotransmitters .
Some evidence also suggests that Endopryl can be metabolized into by-products that may further increase dopamine levels in the brain, such as :
While many different specific mechanisms may be involved in its effects, overall it is believed that Endopryl’s effects come primarily from higher levels of dopamine, serotonin, and noradrenaline throughout the brain.
The symptoms of Parkinson's disease - tremor, stiffness and slow movement - are due to there being less of a chemical called dopamine in your brain. Endopryl works by increasing the effect of dopamine in the brain, and this helps to ease these typical symptoms.
Endopryl should not be used at daily doses exceeding those recommended (10 mg/day) because of the risks associated with non-selective inhibition of MAO. (See CLINICAL PHARMACOLOGY.)
The selectivity of Endopryl for MAO B may not be absolute even at the recommended daily dose of 10 mg a day. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of Endopryl. The selectivity is further diminished with increasing daily doses. The precise dose at which Endopryl becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg a day.
Severe CNS toxicity associated with hyperpyrexia and death have been reported with the combination of tricyclic antidepressants and non-selective MAOIs (NARDIL, PARNATE ). A similar reaction has been reported for a patient on amitriptyline and ELDEPRYL (Endopryl hcl) . Another patient receiving protriptyline and ELDEPRYL (Endopryl hcl) developed tremors, agitation, and restlessness followed by unresponsiveness and death two weeks after ELDEPRYL (Endopryl hcl) was added. Related adverse events including hypertension, syncope, asystole, diaphoresis, seizures, changes in behavioral and mental status, and muscular rigidity have also been reported in some patients receiving ELDEPRYL (Endopryl hcl) and various tricyclic antidepressants.
Serious, sometimes fatal, reactions with signs and symptoms that may include hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations of the vital signs, and mental status changes that include extreme agitation progressing to delirium and coma have been reported with patients receiving a combination of fluoxetine hydrochloride (PROZAC) and nonselective MAOIs. Similar signs have been reported in some patients on the combination of ELDEPRYL (Endopryl hcl) (10 mg a day) and selective serotonin reuptake inhibitors including fluoxetine, sertraline and paroxetine.
Since the mechanisms of these reactions are not fully understood, it seems prudent, in general, to avoid this combination of ELDEPRYL (Endopryl hcl) and tricyclic antidepressants as well as ELDEPRYL (Endopryl hcl) and selective serotonin reuptake inhibitors. At least 14 days should elapse between discontinuation of ELDEPRYL (Endopryl hcl) and initiation of treatment with a tricyclic antidepressant or selective serotonin reuptake inhibitors. Because of the long half-lives of fluoxetine and its active metabolite, at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of treatment with ELDEPRYL (Endopryl hcl) .
Endopryl is an MAO-type B inhibitor, which can increase monoamine (dopamine) levels in the brain and could therefore potentially reverse monoamine deficits in psychostimulant addicts. Transdermal Endopryl was tested in a double-blind, placebo-controlled trial in cocaine-dependent subjects which reported no superior effect of Endopryl to placebo on self-reported cocaine use or benzoylecgonine-free urine samples, which may suggest that MAO-B inhibitors may only have a limited application to treat psychostimulant addiction ( Elkashef et al., 2006 ). The related compound rasagiline, used for the treatment of Parkinson's disease, has not been tested in nonclinical or clinical pharmacological analyses.