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K Spiegel

Publications and source records attributed to K Spiegel.

67 records · Page 4Linked to original sources
PubMed1987

Voluntary beer drinking in rats.

Female Long-Evans rats (N = 30) were tested for individual preference for beer for a 24 h period and then assigned to beer (BR) (N = 15) or control (CT) (N = 15) groups according to preference. BR animals were allowed ad libitum access to beer, food and water; while CT animals were allowed ad libitum access to food and water for a 21 day period. Beer, food and water consumption levels were recorded daily. Animals were weighed every other day. Blood alcohol levels and pattern of drinking (comparison of beer consumption in light versus dark cycles) were measured in a separate set of animals. At the end of 21 days of drinking, beer was withdrawn from the BR group and all animals were observed for withdrawal symptomology. BR animals ate more food than CT animals days 2 through 13, and then ate less than CT on days 17 through 21. BR animals drank more "total water" (drinking water plus water in beer) than CT. Body weights were not affected. Changes in body temperatures and tail flick latency, and notation of hyperactivity, shivering and tremoring during 8 hours of withdrawal indicated that BR animals were dependent on alcohol.

Alcohol Drinking↗
PubMed1985

Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms.

Pretreating rats 24 hr earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P less than .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.

Analgesia↗
PubMed1984

Meptazinol: a novel Mu-1 selective opioid analgesic.

Meptazinol is a unique centrally active opioid analgesic, differing in many respects from the classical opiates or mixed antagonists. Although the overall binding of a series of 3H-labeled opioids is displaced poorly (IC50 values greater than 55 nM), detailed competition studies show that meptazinol inhibits a portion of 3H-labeled opiate and opioid peptide binding quite potently, with IC50 value under 1 nM. Both additional competition studies and saturation studies indicate that the meptazinol-sensitive binding of the 3H-ligands corresponds to the high affinity, or mu-1, binding site. In other binding studies meptazinol has a sodium shift of 8.7, midway between that of morphine (22.5) and naloxone (1.6), suggesting that it is a partial agonist. Naloxonazine treatment 24 hr earlier attenuates meptazinol analgesia in both the mouse writhing and rat tail-flick assays. Spinal transection in the mouse completely eliminates the analgesic activity of high doses of meptazinol in the tail-flick assay, implying a supraspinal mechanism of action in that species. Given at equianalgesic doses, morphine (3.5 mg/kg i.v.) significantly lowers the pO2 over 20 mm Hg and raises the pCO2 over 10 mm Hg as measured in arterial blood samples, whereas meptazinol (10 mg/kg i.v.) has no significant effects on either. Equally important, meptazinol administered with morphine does not reverse the respiratory depressant actions seen with morphine alone, distinguishing meptazinol from other mixed agonist/antagonists. Thus, both the binding and in vivo pharmacological studies are consistent with a mu-1 selective mechanism for the opioid actions of meptazinol.

Analgesia↗
PubMed1983

Analgesic activity of tricyclic antidepressants.

Amitriptyline (median effective dose [ED50] 1.2 mg per kilogram of body weight), imipramine (ED50 2.3 mg/kg), and their demethylated derivatives nortriptyline (ED50 1.9 mg/kg) and desimipramine (ED50 3.2 mg/kg) are active analgesics as indicated by the mouse writhing assay. Although not as potent as morphine (ED50 0.2 mg/kg), the antidepressants were up to 70 times more potent than aspirin (ED50 91 mg/kg). The actions of amitriptyline were not affected by the specific opiate antagonist naloxone but were markedly attenuated in animals whose monoamine levels had been depleted with reserpine. Central mechanisms appear important since amitriptyline (ED50 4.6 micrograms) was potent when administered intracerebroventricularly.

Animals↗
PubMed1983

Biochemical and pharmacological evidence for opioid receptor multiplicity in the central nervous system.

Evidence from a variety of experimental models has suggested the existence of mu 1, mu 2 and delta binding sites for morphine and the enkephalins in the central nervous system. Additional biochemical experiments now support this concept of a common high affinity site for opiates and opioid peptides. Mu sites have now been implicated in a number of pharmacological actions, including supraspinal analgesia, prolactin release, and catalepsy, but not in others (spinal analgesia, respiratory depression, and the guinea pig ileum). The hypothesis of mu 1 sites was supported by the unique opioid meptazinol, which selectively bound to mu 1 sites. As expected from its mu 1 binding selectivity, its analgesic actions in the mouse, localized supraspinally, were antagonized by the selective mu 1 antagonist naloxonazine and it had no respiratory depressant actions. Other binding studies suggested the presence of discrete SKF10,047-selective (KD approximately 5 nM) binding sites in rat brain which differed from both kappa sites and the previously reported PCP-binding sigma sites. Additional binding and autoradiographical studies have also implied the presence of beta-endorphin, or epsilon, sites in the CNS.

Analgesia↗
PubMed1982

Prolactin and growth hormone release by morphine in the rat: different receptor mechanisms.

Concentrations of prolactin and growth hormone in the serum of rats were significantly increased by morphine. Dose response studies demonstrated that maximum prolactin release required lower doses of morphine than those needed for the maximum growth hormone response. Selective blockade of mu 1 (high affinity) opiate receptor with the irreversible antagonist naloxazone reduced morphine-induced peak concentrations of prolactin by 80 percent while increasing peak growth hormone levels by 250 percent. These results suggest different receptor mechanisms for the opiate modulation of the two hormones. The mu 1 (high affinity) receptor sites appear to mediate the morphine-induced release of prolactin but not growth hormone.

Animals↗
PubMed1977

Free-flow electrophoresis. III. An analytical version for a rapid, quantitative determination of electrophoretic parameters.

An analytical device based on the principle of free-flow electrophoresis is described. Electrophoretic mobility distributions of proteins or cells can be obtained quickly with field-strengths of about 140 V/cm. Up to 100 samples can be tested per hour. The accuracy and reproducibility of the device is illustrated by the example of the serum protein separation. Quantities in the picomole range can be quantitatively evaluated. In the course of mobility measurements of cells and cell mixtures, a reproducibility of +/- 1.4% was obtained. Therefore this device meets both the needs of electrokinetic research and the requirement of routine measurements in clinical diagnosis. Finally, the application of a pH gradient is described and the limitation due to methodical aspects is shown.

Animals↗
PubMedDate not supplied

Different receptors mediate morphine-induced prolactin and growth hormone release.

Morphine has a variety of actions on the release of pituitary hormones in addition to its analgesic actions. In the rat, morphine releases prolactin and growth hormone at doses comparable to those active in the tailflick analgesic assay. Naloxazone selectively inhibits the high affinity (mu 1) binding site and dramatically decreases morphine's analgesic potency for over 24 hours. In an effort to determine the opiate receptor mechanisms of morphine-induced prolactin and growth hormone release, groups of rats were treated with either naloxone or naloxazone and 24 hours later the prolactin and growth hormone response to morphine sulfate determined. Peak prolactin levels in the group treated the previous day with naloxone were very similar to levels in untreated controls. However, the peak prolactin levels in the group that received naloxazone the day before were depressed 80% (p less than 0.005). By contrast, growth hormone levels in the naloxazone-treated animals were actually higher than in the naloxone-treated group. Thus prolactin release, like analgesia, appears to be mediated through high affinity, or mu 1, sites, while growth hormone release is not.

Analgesia↗
PubMedDate not supplied

Detection of 6-acetylmorphine in vitreous humor and cerebrospinal fluid--comparison with urinary analysis for proving heroin administration in opiate fatalities.

The concentrations of morphine and 6-acetylmorphine (6-AM) in urine, cerebrospinal fluid (CSF), and vitreous humor (VH) and the morphine concentrations in blood were determined by gas chromatography-mass spectrometry for 29 fatalities after abuse of heroin either alone or in combination with alcohol and other drugs. 6-AM was found above a quantitation limit of 1 ng/mL in urine in 89% of the cases, in CSF in 68% of the cases, and in VH in 75% of the cases. The 6-AM concentrations in CSF (mean, 10 ng/mL) and VH (mean, 17 ng/mL) were in general much smaller than in urine (mean, 170 ng/mL); therefore, the different pharmacokinetic behavior of the fluids is discussed. There is no uniformity between the three fluids with respect to the presence or absence of 6-AM. Therefore, CSF or VH may be used as complementary or alternative materials to urine in order to prove heroin uptake in opiate fatalities.

Adult↗