opiate narcotics
phenathrenes
phenylheptylamines
phenylpiperidines
partial agonist-antagonists
narcotic antagonists
accidental drug-induced Parkinsonism
   Opiates, derived from the poppy plant, contain alkaloids which activate the brain's endogenous endorphin receptors to produce analgesia, euphoria, and respiratory suppression. Poppy opiates possess a polycyclic phenanthrene nucleus with various substituents that determine the fit into the receptor. Although morphinelike compounds have been found in mammalian brain tissue, it is generally agreed that the enkephalins and endorphins represent the endogenous compounds which poppy constituents mimic. 
   Opiate receptors of several varieties are responsible for the major pharmacologic effects. These subtypes are given Greek names like mu (analgesia, euphoria), sigma (dysphoria, cardiac stimulation), kappa (sedation, spinal cord analgesia, miosis), delta, etc. Antitussive properties, emesis (vomiting), and anticholinergic (constipation) effects also occur, indicating a wide variety of receptor types and actions. The sigma receptor is now surmised to be related to glutamate function.
   Opiate receptors exert effects on synaptic transmission by presynaptically modulating the release of neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, and substance P. The latter compound is a peptide neurotransmitter involved in nociceptive (pain-related) neurons. Opiate receptors act on G-peptides, transmembranal macromolecules linked to post-synaptic intracellular enzymes (such as adenylyl cyclase) or ion channels (such as K+, Ca++). In high doses the opiates cause generalized CNS depression sufficient for surgical anesthesia.
phenathrenes
phenylheptylamines
phenylpiperidines
   Codeine is a mild analgesic which retains agonist activity at other receptor subtypes including those controlling respiration, peristalsis and euphoria. Morphine is among the most potent of the phenanthrene class. The less amphoteric heroin crosses the blood-brain barrier more readily but decomposes into morphine once there. Oxycodone, the main active constituent in Percodan and Percocet, is somewhat less potent. 
   Meperidine (Demerol) is a synthetic drug that has approximately the same analgesic activity as morphine. Methadone, invented by the Nazis and originally named dolophine, is famous for its use in assuaging the heroin withdrawal syndrome. Its half-life is substantially greater than that of heroin, and while it is bound to receptors it blocks newly administered heroin. Its analgesic activity is also approximately equal to morphine's, but it imparts less euphoria. 
   Fentanyl constitutes one of the most potent synthetics, propoxyphene (Darvon) one of the least. Methoxy compounds such as codeine and oxycodone are less susceptible to first-pass reactions (typically conjugation to a glucuronide) and therefore have a higher oral-to-parenteral ratio. Less-amphoteric compounds (compounds with more definite acid or base properties) pass the blood-brain barrier more easily. 
partial agonist-antagonists
   Alteration of the phenanthrene skeleton produces drugs with mixed agonist/antagonist properties at opiopeptin subreceptors. These drugs are being used variously as pain killers, aids in withdrawal from heroin and even alcohol addiction, and (illegally) to increase athletic stamina. Stadol has been used nasally to relieve migraines. Although mixed agonists retain analgesic properties, they often impart dysphoric effects.
narcotic antagonists
   Narcotic antagonists are especially useful in cases of overdose, where they can reverse the CNS depression caused by opiate agonists. Naloxone is the most often used, most effective, and prototypal narcotic antagonist. Naloxone, nalmefene, and nadide are among several other compounds used to antagonize morphine receptors.
   Naltrexone has recetnly been used to reduce the craving for alcohol among recovering alcoholics and heroin addicts (as ReVia).
accidental drug-induced Parkinsonism
   In 1983 a group of heroin users attempted a demerol synthesis and obtained instead a compound called MPTP. The product had a similar appearance and melting point, and they injected it expecting a demerol high. In the brain, MPTP decomposes to MPP which selectively binds to and destroys dopamine receptors. These individuals thus prematurely gave themselves Parkinson's disease. MPP closely resembles paraquat, a defoliant used by the US government, outside US borders, against marijuana.