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A pain-treating opioid, methadone is sold under such brand names as Dolophine. Besides pain relief, the drug is used in maintenance therapy. Methadone is one of the drugs considered highly effective as a single dose has a rapid effect, and maximum effect requires only five days of administration of the drug. Its side effects are not dissimilar to the side effects of common opioids, and may include sleepiness, sweating and vomiting, among others. Its use has no alarming effects save for difficulty in breathing which can be alleviated through the usual mechanisms; these only happen in cases of methadone abuse. It is, however, important to note that higher uncontrolled dosage may result in more detrimental effects including death. In the face of approved effectiveness and high efficacy, the use of Methadone for treatment of opiate addiction has received a backlash from different expert quarters. On this note, some researchers have mentioned that the drug fails to function towards curbing the addiction, but only redirects it to authorized channels (Hong, Peter & Peter, 299). Regardless, the existing body of research indicate that the drug is continually being used for the same purpose which renders the former standpoint somewhat questionable. The following report examines the existing body of research on methadone especially concerning its pharmacology. To this effect, three pharmacological elements including mechanism of action, metabolism, and administration route will be profoundly considered.  


In summary, research indicates that Methadone acts through binding of the µ-opioid receptor (Hong et al. 2009). However, it also interacts with NMDA ionotropic glutamate receptor. It is important to note that the most of the aspects of Methadone action largely depend on the differences in people. According to Elefritz et al. (84), the drug is mostly orally administered. Also, unlike other opiates, withdrawal period from the use of Methadone can last as long as two weeks to months. Such factors as drug history, renal and metabolic system dysfunctions, and body weight are central to the rate of excretion and subsuming metabolism of Methadone.

Action mechanism

Methadone exists in a variety of isomers of open chain opioids like levopropoxyphene among others. Some of the common sources of methadone include Levomethadone and Dextromethadone. While the former is a full µ-opioid agonist, the latter has absolutely no impact on the opioid receptors (Kharasch 125). However, Dextromethadone attaches to N-methyl-D-aspartate receptor, which makes it an antagonist receptor with reference to glutamate. Contemporary research has determined that methadone relieves neuropathic pain in rodent given its success in rat models through the antagonism of N-methyl-D-aspartate receptor (glutamergic NMDA). Hong et al. (299) and Kharasch (127) acknowledges the critical role that the NMDA receptors play with respect to memory formation and modulation of prolonged excitation. In fact, a study of such NMDA antagonists like ketamine, detxtromethorphan (DXM), ibogaine, and tiletamine is ongoing especially concerning the part they play in restricting opioid tolerance. The studies also aim at exploiting this property to eliminate withdrawal or addiction through interfering with memory circuitry. Indeed it has been suspected that acting as an NMDA is one of the mechanisms through which methadone increases opioid tolerance and reducing any possible craving. It is on such grounds that Elefritz et al. (86) adds a voice to the approval of methadone for treatment or significant relief of neuropathic pain. According to similar studies, d-methadone (dextrorotary form of methadone) possesses NMDA antagonist properties apart from the fact that it is free from opioid activity. As such, Elefritz et al. (84)’s research shows that it exhibits analgesic properties from the experiments that have been done in the past. In some of those studies, Methadone was used as a potent nicotinic acetylcholine receptor antagonist in the specimen rats which implies that it could be expressed in the embryonic kidney cells in human beings. It is critical to point out that while this sums up the existing information concerning the mechanism of action of Methadone, a myriad research is underway which could widen the narrative and unearth several other data in this line.

Methadone Metabolism

According to Hong et al. (299) Methadone exhibits higher fat solubility coupled with slow metabolism, which implies that it lasts longer compared to morphine-based medications. Besides, its typical elimination half-life rangers between 15 and 60 hours with the average falling at 22 hours. However, depending on the status (properly functioning or unhealthy) of the metabolic system, the metabolism rates vary significantly from one individual to the other. In particular, while in others it is only four hours, others can take up to 130 or 190 hours. Other experts have pegged this variability to the inherent distinction in cytochrome enzymes production (Hong et al. 299; Kaharsch 131). Similarly, there is a list of substances that influence the enzymes, thus, affecting the half-life of methadone. Regardless, it is important to note that a longer half-life facilitates Opioid maintenance and detoxification programs by allowing for safe administration (once a day). Conversely, people with faster metabolism of Methadone may require an administration frequency of up to twice per day for maximum effect while, at the same time, working towards evading the adverse effects that may come with such frequent administration. Longer half-life may also lower the total number of doses in certain patients. Kharasch (134) presents N-demethylation by CYP3A4 both in the intestine and liver as the primary metabolic pathway for Methadone. The products of the N-demethylation includes 3-diphenylpyrrolidine (EDDP), 2-ethylidene-1, and 5-dimethyl-3.

Administration Route

As had been mentioned, the chief, and common administration route of Methadone is through the mouth, in a racemic solution. Higher production costs, however, are gradually outfacing the single-isomer form of methadone according to Elefritz et al. (86). In spite of the preferred from of administration, the drug exists in sublingual tablets, the traditional pill, and two other drinkable formulations used in accordance with the requirements of the patient. However, the liquid form of this drug is more common given that it is allows for minimal changes in dosage. In the same vein, Methadone is still effective when administered via injection just as it is when administered orally. In fact, Elefritz et al. (88) notes that the drug is free of ‘rush’ that is synonymous with such strong opioids like hydromorphone and morphine. The justification for this behavior is that Methadone has an unparalleled volume of distribution which expedites its diffusion into the body tissues especially the fatty tissues (Hong et al. 299). The maximum blood concentration is possible whether the drug is administered orally or through injection. On that note, Hong et al. (299) adds that the primary justification for the preference of oral administration is that it is safe, simple, and excludes Methadone from the list of drugs that are abused through injection.

Caution is advised when administering Methadone through injection since the act may result in swollen, bruised, or collapsed veins among other detrimental impacts (Hong et al. 299). In most of the cases, Methadone pills have talc whose injection may result in several tiny particles in the bloodstream that may cause a blizzard of minor blood clots. While there is no documented instances of instant culmination of these tiny clots into a larger blood clot, the fact that the clots cannot be filtered implies that they gradually accumulate over time. Due to circulation, these tiny clots may have adverse impacts in the eyes and lungs, and may even lead to pulmonary hypertension (Hong et al. 304). Methadose, a brand of Methadone, is strictly prohibited for injection due to such reasons. Even then, it has always been injected in overly diluted concentrations, which have resulted in cases of cardiac arrest among some of the patients (Elefritz et al. 87). Also, it is on such grounds that most of the information leaflets in Methadone packs strictly recommend oral administration for tablets, and warns of potential harm from any other mode of administration. Conclusively, the existing information on Methadone indicates its importance and effectiveness in pain alleviation, among other uses. Therefore, it is pivotal to understand the pharmacology of the drug for proper use and avoidance of the potential detrimental impacts that may accompany improper usage of the drug.

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