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Article Summary

Synthetic Narcotics

In contrast to the pharmaceutical products derived from opium, synthetic narcotics are produced entirely within the laboratory. The continuing search for products that retain the analgesic properties of morphine without the consequent dangers of tolerance and dependence has yet to yield a product that is not susceptible to abuse. A number of clandestinely produced drugs, as well as drugs that have accepted medical uses, fall within this category.


Introduced as an analgesic in the 1930s, meperidine produces effects that are similar, but not identical, to morphine (shorter duration of action and reduced antitussive and antidiarrheal actions). Currently it is used for pre-anesthesia and the relief of moderate to severe pain, particularly in obstetrics and post-operative situations. Meperidine is available in tablets, syrups, and injectable forms under generic and brand name (Demerol, Mepergan, etc.) Schedule II preparations. Several analogues of meperidine have been clandestinely produced. During the clandestine synthesis of the analogue MPPP, a neurotoxic by-product (MPTP) was produced. A number of individuals who consumed the MPPP-MPTP preparation developed an irreversible Parkinsonian-like syndrome. It was later found that MPTP destroys the same neurons as those damaged in Parkinsons Disease.


A close relative of methadone, dextropropoxyphene was first marketed in 1957 under the trade name of Darvon. Oral analgesic potency is one-half to one-third that of codeine, with 65 mg approximately equivalent to about 600 mg of aspirin. Dextropropoxyphene is prescribed for relief of mild to moderate pain. Bulk dextropropoxyphene is in Schedule II, while preparations containing it are in Schedule IV. More than 150 tons of dextropropoxyphene are produced in the United States annually, and more than 25 million prescriptions are written for the products. This narcotic is associated with a number of toxic side effects and is among the top 10 drugs reported by medical examiners in drug abuse deaths.


First synthesized in Belgium in the late 1950s, fentanyl, with an analgesic potency of about 80 times that of morphine, was introduced into medical practice in the 1960s as an intravenous anesthetic under the trade name of Sublimaze. Thereafter, two other fentanyl analogues were introduced: alfentanil (Alfenta), an ultra-short (5-10 minutes) acting analgesic, and sufentanil (Sufenta), an exceptionally potent analgesic (5 to 10 times more potent than fentanyl) for use in heart surgery. Today, fentanyls are extensively used for anesthesia and analgesia. Duragesic, for example, is a fentanyl transdermal patch used in chronic pain management, and Actiq is a solid formulation of fentanyl citrate on a stick that dissolves slowly in the mouth for transmucosal absorption. Actiq is intended for opiate-tolerant individuals and is effective in treating breakthrough pain in cancer patients. Carfentanil (Wildnil) is an analogue of fentanyl with an analgesic potency 10,000 times that of morphine and is used in veterinary practice to immobilize certain large animals.

Illicit use of pharmaceutical fentanyls first appeared in the mid-1970s in the medical community and continues to be a problem in the United States. To date, over 12 different analogues of fentanyl have been produced clandestinely and identified in the U.S. drug traffic. The biological effects of the fentanyls are indistinguishable from those of heroin, with the exception that the fentanyls may be hundreds of times more potent. Fentanyls are most commonly used by intravenous administration, but like heroin, they may also be smoked or snorted.


The effort to find an effective analgesic with less dependence-producing consequences led to the development of pentazocine (Talwin). Introduced as an analgesic in 1967, it was frequently encountered in the illicit trade, usually in combination with tripelennamine and placed into Schedule IV of the CSA in 1979. An attempt at reducing the abuse of this drug was made with the introduction of Talwin Nx. This product contains a quantity of antagonist (naloxone) sufficient to counteract the morphine-like effects of pentazocine if the tablets are dissolved and injected.


While butorphanol can be made from thebaine, it is usually manufactured synthetically. It was initially available in injectable formulations for human (Stadol) and veterinary (Torbugesic and Torbutrol) use. More recently, a nasal spray (Stadol NS) became available, and significant diversion and abuse of this product led to the 1997 control of butorphanol in Schedule IV of the CSA. Butorphanol is a clear example of a drug gaining favor as a drug of abuse only after it became available in a form that facilitated greater ease of administration (nasal spray vs. injection).

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