In 1803, Friedrich Serturner isolated morphine from opium and presented for the first time that a "single purified chemical substance could account for the pharmacological effects of a natural product". This was the beginning of the pharmacological industry, as we know it today.

In the 1980s, the Bayer Co introduced heroin, an opiate derivative with two acetyl groups (COCH3) added. The acetyl groups would add at R1 and R2 on the opiate alkaloid structure. At R4 hydrogen (H+) would be substituted for the methyl group (CH3). Because this insidious drug can be made on the street by treating raw opium with acetic anhydride, and because of its powerful addicting effects, the early chiropractors inadvertently began an unwanted war with the medical profession, which advocated heroin to the extent that it became common place and found in drug stores. However the damage was done, and although eventually the addictive properties of opiates became realized and made illegal, the quest for nonaddictive agents with similar properties began. Today such famous analgesics such as Demerol (merperidine), codeine (methylmorphine), oxymorphone, Lortabs or Vicodin all exert signs of "tolerance addiction." The elusive goal of finding a non-addictive, but powerful pain control agent is still being researched today with the same types of errors (such as the illusion of acupuncture) being touted by the medical profession.

Most opiates or opiate-like drugs and chemicals exist in at leas two optical enantiomers. Mirror-image molecules that differ from one another only in the way that the atoms are oriented in space; their chemical composition is identical but, like left and right hands, each cannot be superimposed on the other. It is this sterospecificity that tells us the "handedness" of the opiate-like agents or synthetic drugs. Because these optical enantimers rotate a plain of polarized light in two different directions, they can easily be distinguished. Most often only the isomer that rotates the plane or polarization to the left, the levorotatory isomer, will relieve pain, induce euphoria, and elicit nausea among other effects.

These opiate agonists can easily be reacted upon to yield antagonists. The substitution of an allyl group (CH2-CH=CH2) for the methyl group (CH3) on the nitrogen of morphine yields "nalorphine," the potent antagonist capable of blocking all pharmacological effects of morphine and its derivatives. These antagonists react very fast and by blocking the specific receptor site used by the agonists.

The mechanism of the antagonists can be postulated by understanding the Snyder "model" and the effect sodium has on the receptor. In the Snyder model, sodium would fix a specific reactor to the antagonist conformation, thus creating a low affinity for the agonists. The converse is true, if sodium is removed; the receptor will have a high affinity for the agonists. As long as sodium is bound to a receptor site, its affinity for the agonist will be low and the antagonist will bind to the receptor site, thus reducing the number of receptors that are capable of mediating the agonist effects. It is know that the fluid bathing the brain is rich in sodium. The agonist receptors in the brain normally exist in the sodium-binding state. It is also known that antagonists have a much greater potency then agonists in living organisms.

Summarization follows:

Because neurotransmitters act at synapses, the agonist receptor is thought to function very much like a receptor site for a natural neurotransmitter substance in the brain. Moreover, the existence in all vertebrates of specific opiate receptor sites strongly indicates the existence of a natural morphine-like substance in the brain. Huges and Kosterlitz isolated a morphine-like factor from the brain of pigs. It consisted of two closely related short peptides--both made up of five amino acid units. They coined the name or this morphine-like substance "enkephalin."

Originally, Rabbi Simantov and Snyder purified the two peptide chains from the brain of cattle. It is now known that, the enkephalins are neurotransmitters of specific neuronal systems in the brain, which medicate the sensory information having to do with pain and emotional behavior. Furthermore, the enkephalins appear to be localized in nerve endings.

The release of neurotransmitter from a nerve terminal is triggered by the depolarization of the terminal membrane, which occurs at a time when the nerve impulse propagates to the end of the nerve fiber. The greater the depolarization of the membrane, the greater the amount of transmitter released. Neurons that release enkephalin form their synapses on the terminals of excitatory neurons. As enkephalin is released at such synapses, it binds to the opiate-like receptors on the excitatory nerve terminal, thereby increasing the conductance of sodium across the membrane of the terminal, partially depolarizing it. When a nerve impulse finally reaches the terminal, the net depolarization generated by it would be reduced; therefore there is a corresponding decrease in the total amount of excitatory transmitter released. The action of enkephalin would itself be excitatory, since it increased the flow of sodium across the nerve terminal membrane. Yet, the ultimate effect on the cell receiving the excitatory nerve terminal would be inhibitory, because the amount of excitatory transmitter effecting its activity would be reduced. This enkephalin inhibitory system may modulate the activity of the ascending pain pathways (neospinothalmic and paleospinothalmic in vertebrates, also known as, the anterior and lateral spinothalamic tracts) in the spinal cord and brain. Agonists act by binding to unoccupied enkephalin receptors, so as to potentate the effects of the system.

Summary:

"Why does this magnificent applied science which saves work and makes life easier, bring us little happiness? The simple answer runs, because we have not yet learned to make sensible use of it." Albert Einstein 1931