Pentazocine: Biological Mechanisms, Clinical Applications and Side Effects
Pentazocine is an opioid analgesic drug available in some European countries and in drug combination products in the United States.1 It was developed by the Sterling Drug Company, Sterling-Winthrop Research Institute of Rensselaer, New York in 1958.2 By mid-1967, pentazocine was being sold in Mexico, England and Argentina, and it was finally approved by the United States Food and Drug Administration (FDA) after favorable reviews following testing on 12,000 U.S. patients.2 During the 1980s, pentazocine was sold in the U.S. primarily in combination with the antihistamine tripelennamine, was known familiarly as “T’s and Blues” and was used as a substitute for heroine.1 Today, pentazocine is sold under several brand names, such as Fortral, Talwin, Talwin NX (with naloxone), Talwin PX (without naloxone), Fortwin (injectable form) and Talacen (with acetaminophen).2 Because of pentazocine’s role in treating moderate to severe pain, anesthesia providers should have thorough knowledge of its biological mechanisms, clinical uses and adverse effects.
The molecular formula for pentazocine is C19H27NO3 and it may exist as one of two enantiomers named (+)-pentazocine and (–)-pentazocine.2 (–)-pentazocine, which is the version with analgesic effects,3 is an agonist at κ-opioid receptors, while (+)-pentazocine may exert psychotomimetic and dysphoric effects at high doses due to σ-opioid receptor agonism.4 Additionally, pentazocine has weak antagonist actions at the μ-opioid receptor.5 Pentazocine is approximately one third as potent as morphine following intramuscular administration.6 It is well-absorbed in the gastrointestinal tract, allowing it to be distributed throughout the body after oral administration.7 It is metabolized in the liver and has a half-life of approximately 12 hours, with a duration of action of about three to five hours.6 Then, it is excreted mainly in the urine.6 Pentazocine is mainly unique from other opioid drugs in its function as an agonist-antagonist.
Pentazocine can be used in a variety of clinical settings. It can be administered by subcutaneous, intramuscular or intravenous injection; the usual dose is 30 to 60 milligrams of pentazocine every three to four hours.2 It is also available in 25 milligram pills.2 Pentazocine has been reported to provide effective analgesia in a range of animal species, including humans.8 It can also be administered to induce preoperative sedation6 or in conjunction with general or regional anesthesia.3 Unlike other opioid drugs, pentazocine does not cause bradycardia (i.e., slow heart rate).4 As an agonist-antagonist, it has a ceiling effect, meaning that administration of more than approximately 60 to 100 milligrams does not increase risk of respiratory depression or reduce pain.4 Overall, pentazocine is commonly used throughout the perioperative period for analgesia and sedation.
As an opioid, pentazocine is accompanied by several unpleasant side effects, including sedation, confusion, euphoria, agitation, itching, sweating, abdominal bloating, nausea, vomiting and constipation.9 More severe and rare side effects can include confusion, clammy skin, changes in heart rate or blood pressure, sweating or lightheadedness.10 Like other opioids, pentazocine can cause respiratory depression that is reversible by administration of naloxone.6 Furthermore, pentazocine’s antagonistic effects can cause withdrawal symptoms in chronic opioid agonist users.11 Pentazocine is a controlled substance and is classified by the United States Drug Enforcement Administration (DEA) as a Schedule IV drug, meaning that it has medical usefulness and a mild potential for physical and psychological dependency and abuse.9 In some states and countries, pentazocine is classified as a Schedule III drug, with greater abuse and dependency potential.9 Pentazocine’s side effects are similar to those of other opioid drugs, though it may cause more withdrawal symptoms than simple opioid agonists.
Pentazocine is an opioid agonist-antagonist used for perioperative sedation and analgesia. Pentazocine acts as an agonist at κ- and σ-opioid receptors and a weak antagonist at μ-opioid receptors. Its analgesic effects are less potent than morphine, and it does not cause bradycardia that is often found in other opioid drugs. Pentazocine exhibits a ceiling effect in regards to respiratory depression and analgesia. Its side effects are similar to those of other opioids—nausea, vomiting, euphoria, gastrointestinal issues and respiratory depression—and it can also cause withdrawal symptoms in people who regularly use opioid agonists. Though pentazocine has a lower abuse potential than other opioid drugs, anesthesia providers should consider its potentially adverse side effects before prescribing it to their patients.
1. Reuvers M, Schaefer C. Analgesics and anti-inflammatory drugs. In: Schaefer C, Peters P, Miller RK, eds. Drugs During Pregnancy and Lactation (Second Edition). Oxford: Academic Press; 2007:28–56.
2. Current JD. Pentazocine. Pharmacology for Anesthetists: Anesthetics and Adjuvants. Mainz, Germany: PediaPress; 2020:452–456.
3. Pentazocine. PubChem Database. Web: National Center for Biotechnology Information; 2020.
4. Koyyalagunta D. Chapter 113—Opioid Analgesics. In: Waldman SD, Bloch JI, eds. Pain Management. Philadelphia: W.B. Saunders; 2007:939–964.
5. Pentazocine (HMDB0014790). The Human Metabolome Database. Web 2020.
6. Malamed SF. Intramuscular Sedation. In: Malamed SF, ed. Sedation (Fifth Edition). Saint Louis: Mosby; 2010:132–162.
7. Pentazocine. DrugBank February 20, 2020; https://www.drugbank.ca/drugs/DB00652.
8. Flecknell PA. Analgesia and Post-operative Care. In: Flecknell PA, ed. Laboratory Animal Anaesthesia (Third Edition). San Diego: Academic Press; 2009:139–179.
9. Pentazocine. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; April 25, 2019.
10. Mayo Clinic. Pentazocine (Injection Route). Drugs and Supplements February 1, 2020; https://www.mayoclinic.org/drugs-supplements/pentazocine-injection-route/side-effects/drg-20074265.
11. Malamed SF. Intramuscular Sedation. Sedation (Sixth Edition): Mosby; 2018:134–163.