Morphine drug discrimination

In withdrawn morphine-dependent rhesus monkeys, the morphinones exacerbated withdrawal at very low doses. Withdrawal effects persisted even after morphine administration (3 mg/kg, 6 hourly) was resumed [23]. Self-administration and drug discrimination studies in rhesus monkeys were also included in this report. In the drug discrimination assay the codeinones all generalised to codeine. The 4 -bromo- and 4 -methylcinnamoylaminodihydrocodeinones (40b, 40c) were also self-administered but at rates that were below those of codeine [22]. These results confirmed the MOR partial agonist character of the codeinones. 

In the drug-discrimination paradigm (see ref. 19 and Note 3), laboratory animals learn to recognize the presence of a certain drug (such as nicotine, morphine, LSD, A -THC) and express the discrimination between the drug under investigation and a control substance (placebo) in a two-choice situation, where the correct choice is rewarded. 

FIG. 2. Comparison of the discriminative stimulus properties of LSD, morphine, and methadone when injected into the DRN of the rat. Rats were trained to discriminate LSD (120 ng/kg s.c.), cannulae implanted, and generalization from peripheral to central administration determined over a variety of doses of each drug. (Redrawn from the research of Rosecrans and Glennon, ref. 59.) A, I.C. saline, , I.C. morphine in morphine trained rats, O, I.C. saline, , I.C. LSD in LSD trained rats, , I.C. saline, , I.C. methadone in methadone trained rats. 

Dykstra, L. et al., Discriminative stimulus properties of cocaine alone and in combination with buprenorphine, morphine and naltrexone, Drug Alcohol Depend., 30, 227, 1992. 

An alkaloid pain reliever, morphine, is an often abused drug. Chronoampero-metric MIP chemosensors have been devised for its determination [204]. In these chemosensors, a poly(3,4-ethylenedioxythiophene) (PEDOT) film was deposited by electropolymerization in ACN onto an ITO electrode in the presence of the morphine template to serve as the sensing element [204], Electrocatalytic current of morphine oxidation has been measured at 0.75 V vs AglAgCllKClsat (pH = 5.0) as the detection signal. A linear dependence of the measured steady-state current on the morphine concentration extended over the range of 0.1-1 mM with LOD for morphine of 0.2 mM. The chemosensor successfully discriminated morphine and its codeine analogue. Furthermore, a microfluidic MIP system combined with the chronoamperometric transduction has been devised for the determination of morphine [182] with appreciable LOD for morphine of 0.01 mM at a flow rate of 92.3 pL min-1 (Table 6). 

Fedotozine (Jo-1196,170), which is structurally related to the acyclic k agonists, has in vivo antinociceptive effects on duodenal pain that appear to be mediated by peripheral k opioid receptors, but the compound is inactive after central administration (544). In binding assays (in dog myenteric plexus), however, this compound exhibits similar affinity = 0.3-0.8 jM) for all three types of opioid receptors (545). Unlike other k agonists, fedotozine does not induce diuresis after either s.c. or in-tracerebroventricular (i.c.v.) administration (546). Fedotozine also fails to substitute for either U50,488 or morphine in animals trained to discriminate these drugs (547). The main effects demonstrated for fedotozine have been in the gastrointestinal tract (seeRef 548 for a detailed review of the pharmacology of fedotozine), and therefore this compound has... 

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