Kappa agonists dynorphins

It is of historical interest to note that the disclosure of U-50488 occurred at roughly the same time as two chemically unrelated compounds which behave as poorly selective kappa agonist analgesics. These are the benzodiazepine, tifluadom (6) [17] and the amino-terminal nonapeptide fragment of dynorphin, Dyn (1-9), (7) (kappa A) = 0.21 nM, mu K = 3.6 nM delta K, = 3.2 nM) [18], which is thought to be the endogenous kappa opioid agonist. 

There are three families of opioid receptors mu, delta, and kappa. Each type of receptor has a different affinity for specific opioids, and specific effects when activated. Each opioid receptor can cause analgesia mu-agrafists (such as morphine) also tend to cause more dependency, while kappa-agonists such as the endogenous opioid dynorphin cause more dysphoria. 

Preliminary data indicate that in the reserpinised rat or MPTP marmoset, the enkephalin agonist (SNC80) reduces PD-like symptoms without causing increased activity, i.e. no trend to dyskinesias. Enadoline, a dynorphin-like kappa opioid agonist also has similar effects in the same models. Whether it would be similar in humans remains to be seen. 

Mu receptors are almost always located proximally, on the presynaptic side of the synapse. The periaqueductal gray is the region containing the most mu receptors, but they are also found in the superficial dorsal hom of the spinal cord, the external plexiform layer of the olfactory bulb, the nucleus accumbens (an area deeply implicated in the process of addiction), in some parts of the cerebral cortex, and in some of the nuclei of the amygdala. Mu receptors avidly bind enkephalins and beta-endorphin, but they have a low affinity for dynorphins (primarily a kappa receptor agonist).6... 

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