PCP (phencyclidine, or 1-phenyl-cyclohexylpiperidine (figure 1, below) is the best known representative of the class of drugs collectively known as arylcyclohexylamines. Two other members of this structural class are ketamine and tiletamine. PCP was formerly used as a surgical anesthetic in both humans and veterinary practice, but it is not currently manufactured, and has been placed under Schedule II of the Controlled Substance Act in the US. Tiletamine is dispensed as a mixture with the benzodiazepine zolazepam (Telazol) as large animal tranquilizer, and is a Schedule III drug. Ketamine is used in both veterinary and human anesthesiology, although its predominant use in the US is in animals. Currently it is not scheduled under federal law, but will most likely be added to schedule II or III within the next two years.
The other compounds shown in figure 1: PCPy, TCP, and PCE, as well as TCPy (the thiophene analog of PCPy), are potent PCP analogs that have appeared on the illicit market in the US and subsequently been added to Schedule I of the Controlled Substance Act. Reportedly at least 30 other unscheduled analogs that have been produced by clandestine sources.
This review covers the synthesis and pharmacology of the close structural derivatives of PCP. However, there are several other classes of compounds that bind to the same receptor as PCP and produce PCP-like effects. All together, these classes contain literally hundreds of potentially active drugs.
Five other structural classes of compounds that produce potent PCP-like effects are shown in figure 2 , below. All of them are known to bind at the same receptor site as PCP, and share at least some of its pharmacological profile (ref. 42). These compounds will not be discussed here, but are pictured to illustrate the diversity of structures having similar effects to PCP.
- Benz(f)isoquinolines (ref. 43)
- Propanolamines, e.g. 2-MDP
- Benzomorphans, e.g. Pentazocine (Talwin). These compounds have been used as analgesics and also have affinity for additional receptors. See information regarding sigma affinity below.
- Dioxolanes, e.g. Dexoxadrol and Etoxadrol (ref. 42)
- Tricyclics such as MK-801 (Dizocilpine). This class includes some of the most potent selective PCP receptor ligands known (ref. 38, 44). MK-801 is about 2 to3 times more potent than PCP, and is longer lasting. Animals that have been trained to self-inject PCP will also self-inject this compound, a fact that is proposed to demonstrate "abuse potntial" (ref. 46, 47).