Kappa receptors morphine

Mu and kappa receptor agonists have been shown to affect central dopaminergic activity in rodents in vivo and in vitro [78, 79]. This has been investigated with RP 60180 (51), which decreases dopamine (DA) utilization in rat prefrontal cortex and in the striatum (by 30—35 % and 10 % respectively at 1-2.5 mg/kg s.c.) whereas the mu agonist morphine causes a significant increase (90-150% and 30 40% respectively at 5 mg/kg), an effect which is abolished by RP 60180 (1 2.5 mg/kg) [80]. 

In the above discussion on the mu/kappa receptor selectivity of the U-50488 (5) series, the steric properties of the tertiary amine and the distance between the amide and the aromatic ring were cited as important factors. This has been exploited by the Upjohn company to give the arylformamide-dimethyl-amine derivative (52) which is an analgesic in the mouse tail flick test (ED50 = 0.2 mg/kg s.c.) and causes mu-opioid like side-effects such as Straub tail, arched back and increased locomotor activity [81]. These behavioural effects and the association constant for the morphine receptor of compound... 

Delta and kappa receptors can also contribute to analgesia, particularly at spinal level. Although morphine also acts on kappa and delta sites but it is not clear that up to what level they contribute in its analgesic action. 

Isom et al. mentioned endogenous generation of CN and the possibility that CN may function as a neuromodulator in a manner similar to nitric oxide. Brain CN levels are increased by hydromorphone and the effect is blocked by naloxone. Undifferentiated rat pheochromocytoma cells also show increased CN production in response to hydromorphone or morphine. Since PC 12 cells have mainly kappa opiate receptors and no mu receptors, hydromorphone probably acts through kappa receptors to increase CN release. ... 

Morphine is a naturally occmring alkaloid from the opium poppy seed. Modern formulations employ synthetic morphine. Major and minor sites of morphine activity include spinal and supraspinal opioid receptors. Morphine binds to and activates mu, kappa and delta receptor subtypes. 

Buprenorphine hinds to mu, kappa, and delta opioid receptor suhtypes. It has a partial agonist activity at mu receptors and an antagonist activity at kappa receptors. Less is known about the activity of buprenorphine at delta receptors. Buprenorphine is more lipophilic than morphine and penetrates the blood-brain barrier more easily and has a rapid onset of effect. 

The relative extent of the unwanted effects caused by selective agonists at the different opioid receptors is of great importance in determining if non-mu opioids will have better spectra of actions as compared to morphine. However, there are good indications that the kappa and delta receptor agonists cause less respiratory depression than mu... 

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