Dependence deltorphins

I.c.v. and i.t. administration of the 5 opioid agonist deltorphin II in rodents inhibits diarrhea and colonic bead expulsion in a dose-dependent manner but does not delay small intestine transit time. 5 agonists have been found to mediate mainly antisecretory effects and influence gut motility only marginally. These effects can be antagonized by pretreatment with NTI (Shook et al. 1989). 

Both D-Met-deltorphin and D-Ala-deltorphins exhibit long half-lives in brain homogenates and plasma, (ti/2 =57 and 130 min for deltorphin and 11/2 =4 and 6 h for D-Ala-deltorphins). The metabolites, generated by metalloendoproteases are represented by the N-terminal penta-, tetra-, and tripeptides. Stability depends on the presence of D-isomer and C-terminal... 

D-Ala-deltorphin-II induces 6-opiate receptor mediated analgesia in frogs [55] and also in the invertebrate land snail (Cepaea nemoralis) [56]. When administered by intrathecal injection in rats, D-Ala-deltorphin-II produces a dose-related inhibition of the tail-flick response (threshold 0.6 nmol/rat). Its inhibitory effect lasts 10 60 min, depending on the dose, and is naltrindole reversible [57]. Wang et al. [25] demonstrated that D-Ala-deltorphin-II inhibited A6 and C fiber evoked responses from nociceptive neurons in the superficial and deeper dorsal horn of the rat medulla. 

The high-affinity GTPase activity in the mouse spinal cord is increased in a concentration-dependent manner by [D-Ala2]deltorphin II [82]. This increase of GTPase activity induced by [D-Ala2]deltorphin II is completely blocked by coincubation with a selective delta opioid receptor antagonist NTB [82]. 

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