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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Sunday, February 20, 2011

The Morphine Rule


The Morphine Rule:

The following features are found in most mu opioid agonists, and together are referred to as the morphine rule. These structural features form the morphine backbone shared by most morphine derived and synthetic opioids. They are for the most part essential for morphine-like activity - as the molecule must sufficiently conform to the shape of the particular receptor it targets. If a drug has affinity for the receptor but fails to conform for a perfect fit, it may fail to elicit a biological response. There are 4 key characteristics of mu-active opioid compounds. Few exceptions apply.

1) A tertiary nitrogen with a small alkyl substituent
2) A quarternary carbon
3) A phenyl ring or its equivalent attatched to the quarternary carbon
4) A 2 carbon spacer between the quarternary carbon and the tertiary nitrogen


Structural Configuration & Receptor Docking


An opioid molecule binds with its target receptor like a key fits into a lock. In order for morphine (or any other opioid) to bind to a particular receptor, its molecular structure must show some degree of conformity to the structure of that receptor. Furthermore, the molecule must possess the structural characteristics required to exert an effect at the receptor; just as many different keys may fit into a lock, not all will turn once inside - When an opioid binds to its receptor and activates a response, it is considered an agonist at this receptor. When an opioid binds to its receptor but fails to induce a response, it is considered to be an antagonist at this receptor.


"The shape of the morphine molecule is crucial to its ability to exactly fit into the active site on the receptor - the 'lock-and-key' mechanism. The benzene group of the morphine molecule fits snugly against a flat section of the receptor protein, whilst the bent neighbouring group of carbon atoms fits into a nearby groove. This allows the positively charged nitrogen atom to attach to a negatively-charged group on the receptor, so locking the two molecules together." (See A2 and A3)


A2
A3

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