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Biomedical subjects

E F Hahn

Publications and source records attributed to E F Hahn.

53 records · Page 3Linked to original sources
PubMed1979

Brain opiate receptor concentrations are increased in adult spontaneously hypertensive rats.

The saturable binding of 3H-naltrexone in the brains of eight week old spontaneously hypertensive rats (SHR) is about twice that measured in corresponding normotensive WKY rats. This increase is dependent on age since in three and four week old SHR and WKY rats no difference in binding is observed. Scatchard analysis of the saturation curves for the adult animals revealed that the change in binding is due to an increase in the number of binding sites and does not reflect a difference in binding affinity. The increase in opiate receptor content of SHR rats coincides with the appearance of elevated blood pressure in these animals, and supports a concept in which an interaction between the endorphins and the endocrine system may be involved in the mechanisms controlling hypertension.

Aging↗
PubMed1977

The agonist and antagonist properties of N-allylenkephalins.

The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.

Allyl Compounds↗
PubMed1977

Orientation of the oxygen atom at C-6 as a determinant of agonistic activity in the oxymorphone series.

The kinetics of various oxymorphones, their 6-methylene analogs and the 6-hydroxy-epimers corresponding to naloxone and naltrexone have been studied in the longitudinal muscle strip of the guinea-pig ileum. Substitution of the oxygen at C-6 by amethylene group slightly increased antagonistic activity of the resulting structures, without significantly influencing agonistic activity relative to the parent compound. The alpha-orientation of the hydroxy group at C-6 enhanced the agonistic property of both naloxone and naltrexone. The beta-compounds, however, were pure antagonists, with potencies similar to those of the parent keto structures.

Animals↗
PubMed1977

Morphine metabolism in opiate dependent and normal men by double isotope techniques.

A mixture of morphine-63H and morphine-N-14CH3 was administered to an opiate dependent and to a normal male subject. In both subjects the urinary excretion of radioactivity was rapid and exceeded 85% of the dose over 72 hours. The extent and time pattern of N-demethylation differed in the two subjects with N-demethylation of morphine being slower and less in the opiate addict. The use of the double isotope technique in detecting small changes in morphine metabolism is discussed.

Adult↗
PubMed1976

Dose related changes in tissue morphine concentration.

Rats were injected with morphine-6(3)H diluted with increasing amounts of non-radiolabelled morphine. The entry of the isotope into the brain and various tissues was measured by combustion in a tissue oxidizer. The relative distribution of morphine between the blood and brain remained constant at about 5.5:1 over the range of doses studied (0.07 - 10.0 mg/kg). No dose related differential effects on morphine uptake were evident in central tissues, with the exception of the hypothalamus which exhibited a disproportionately greater uptake. Among the noncentral tissues, kidney and liver showed the greatest dose related increases in uptake.

Animals↗
PubMed1976

An evaluation of the hot plate technique to study narcotic antagonists.

The mouse hot plate model, with slight differences from the way it is used to study narcotic analgesics, was evaluated as a method for determining the oral effectiveness, relative potency and duration of action of two standard narcotic antagonists, naloxone and naltrexone, and a new agent, 6-desoxy-6-methylene-naltrexone (ORF 11676). Naltrexone and ORF 11676 were found to be more effective orally than naloxone. Naltrexone and ORF 11676 were equipotent by 3 routes of administration and both were more potent than naloxone. Naloxone produced a significantly shorter duration of action than the other two drugs. It was concluded that the mouse hot plate method, used to detect and characterize the activity of narcotic antagonists, provides information compatible with that obtained in other species, including man.

Animals↗
PubMed1975

Narcotic antagonists. 4. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists.

A series of new narcotic antagonists has been synthesized by modifying the C-6 carbonyl group in naloxone (Ia) and naltrexone (Ib). New functional units were introduced by reaction with various phosphorus and sulfur ylides and alkyllithium reagents. The activity of the new compounds were measured by the hot-plate and tail-clip tests after oral administration to mice. The majority of the new narcotic antagonists exhibited oral potencies considerably superior to the parent compounds, with 6-methylene derivatives IIa and IIb showing the most impressive increases.

Analgesia↗
PubMed1975

Preparation and evaluation of a sustained naloxone delivery system in rats.

The use of a non-biodegradable polymer system to provide a sustained release of the narcotic antagonist naloxone in rats is described. The kinetics of morphine analgesia (measured by the hot-plate test) in the presence of the naloxone implant, and the urinary excretion of radiolabeled naloxone were measured. The shift of the morphine dose-response curve to the right is expressed in terms of dose ratios, which were calculated from the ED50 values for morphine obtained 9 days before, and 1, 8, 15, 22 and 29 days after implantation of the polymer. Our experiments indicate that effective levels of antagonist were maintained for 3-4 weeks after implantation of a polymer system containing 16 mg of naloxone. After 29 days, more than 95% of the absorbed drug had been released, with 16% of the implanted radioactivity appearing in the urine. These results demonstrate the feasibility of using a sustained release form of a narcotic antagonist to block the effects of morphine.

Animals↗
PubMedDate not supplied

Naloxonazine, a potent, long-lasting inhibitor of opiate binding sites.

Naloxazone, the hydrazone derivative of naloxone, has proven useful in studies of opiate binding site heterogeneity both in vivo and in vitro based on its long-acting inhibition of high affinity, or mu1, binding sites. However, the need for high doses of naloxazone to inactivated the mu1 sites raised the possibility that its actions might result from lower concentrations of a more active compound. We now present evidence suggesting that this more active compound is the azine derivative of naloxone. In acidic solutions, approximately 35% of naloxazone, spontaneously rearranges to the azine, naloxonazine. Unlike naloxazone, naloxonazine is relatively stable in solution. It does not appreciably dissociate into naloxone and naloxazone and no additional compounds can be detected. Under assay conditions under which no azine formation can be detected, no inhibition of binding of either 3H-dihydromorphine or 3H-DADL is found after incubating tissue with naloxazone at concentrations up to 2000 nM followed by extensive washing. Naloxonazine, on the other hand, produces a potent, dose-dependent inhibition of binding which is resistant to washing. Despite the washes, naloxonazine at 50 nm abolishes high affinity binding with some inhibition seen at concentrations down to 10 nM.

Animals↗