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Biomedical subjects

J M Mayer

Publications and source records attributed to J M Mayer.

At least 73 records · Page 4Linked to original sources
PubMed1988

Metabolic chiral inversion of anti-inflammatory 2-arylpropionates: lack of reaction in liver homogenates, and study of methine proton acidity.

1. Enrichment in the (S)-enantiomers for (R)-flurbiprofen, (R)-naproxen, (R)-suprofen and (R;S)-ibuprofen was investigated in various subcellular hepatic preparations containing coenzyme A. While such preparations were able to form hippuric acid from benzoic acid, the chiral inversion was never seen. 2. Using 2-dimethylaminoethanethiol 2-phenylpropionate (DEPP) as a model acyl thioester, the acidity of the methine proton was investigated by monitoring the proton/deuterium exchange occurring in deuterated solvents using high-resolution n.m.r. The compound was inert up to 22 h in D2O at 37 degrees C and pD 7.4. In pure methanol or a methanol-water mixture, only solvolysis was seen. In contrast, competitive hydrolysis (k = 0.005 h-1) and proton/deuterium exchange (k = 0.09 h-1) were seen in a CD3CN/D2O (50:50) mixture at 37 degrees C. 3. It is speculated that the failure to characterize chiral inversion of 2-arylpropionates in subcellular preparations may be due to the absence of a microenvironment of adequately moderate polarity.

Animals↗
PubMed1988

[Terson's syndrome. Apropos of 7 cases].

We studied seven cases of Terson's syndrome, in association with bleeding in the subarachnoid space caused by rupture of vascular malformation or cranial traumatism. The association of rapid increase of intracranial pressure with subarachnoid hemorrhage could explain the development of a Terson's syndrome. The retinal hemorrhages associated with the vitreous hemorrhage are variable in morphology and topography. Pars plana vitrectomy has been performed in eight eyes with most often good results.

Adolescent↗
PubMed1986

Dual ligand binding of pyridylalkanamides to microsomal cytochrome P-450.

Twelve homologous and regioisomeric pyridylalkanamides were examined spectrally for their binding affinity to cytochrome P-450 in phenobarbital- and 3-methylcholanthrene-induced rat liver microsomes. The pKs values were calculated by the Lineweaver-Burk method and by non-linear analysis using both a one ligand-one acceptor and a one ligand-two acceptor model. The latter model best fits most of the data, confirming that two pKs values exist for most derivatives in the 3-pyridyl and 4-pyridyl series. Structure-binding relationships are discussed. The two binding constants are hypothesized to arise from a dual mode of binding to the ferric ion. At low ligand concentrations, binding to hexacoordinated cytochrome P-450 occurs and involves displacement of an endogenous 6th ligand; at higher concentrations, the ligands bind to the pentacoordinated P-450, resulting in a high-to-low spin shift.

Animals↗
PubMed1986

Familial juvenile parkinsonism with multiple systems degenerations. A clinicopathological study.

An unusual case of familial multisystemic degeneration is reported. Two siblings had juvenile parkinsonism, areflexia, and retinal degeneration of slow progression. The main neuropathological findings in case 1 were pallidoluysian, nigral, dentate, and dorsal columns degeneration. The authors draw a comparison between this case and juvenile parkinsonism, dentato-rubro-pallido-luysian atrophy, and spino-cerebello-nigral degeneration.

Adult↗
PubMed1986

Affinity of pyridylalkylamines for nicotinic, muscarinic and histaminic recognition sites in brain tissue preparations.

The affinity of 15 regioisomeric and homologous pyridylalkylamines was examined in brain preparations for nicotinic, muscarinic, and H1-histaminic binding sites as labeled by [3H]-nicotine, [3H]-dexetimide and [3H]-mepyramine, respectively. Overall, the compounds show a clear selectivity for the nicotinic versus muscarinic binding sites, and a weak affinity for the H1-histaminic sites. Variations in affinity appear to be partly influenced by steric factors (such as position of attachment, length and rigidity of side-chain) and marginally by lipophilicity.

Amines↗
PubMed1985

[Biopharmaceutics of ophthalmic drugs].

The importance of biopharmaceutics in the development of ophthalmic drugs is pointed out. Ophthalmic drugs have to be stable, sterile, well tolerated and effective. The constraints resulting from these requirements limit the number of pharmaceutical presentations. The development of pilocarpine eye drops is taken as an example to illustrate how difficult it is to satisfy Goldmann's criteria of stability, sterility, tolerance, and efficacy simultaneously. A rapid and sensitive ocular tolerance test for the selection of the most favorable formulations is proposed as a means of counteracting the present shortage of screening tests. Additionally, the physiological, physicochemical, and pharmaceutical factors are discussed which can influence the drugs' passage through the cornea and consequently increase or decrease their efficacy. Two examples, taken respectively from the aqueous solutions and lipophilic gels, demonstrate the importance of pharmaceutical and biological availability as well as the present tendency toward optimization in the development of ophthalmic preparations.

Biopharmaceutics↗
PubMed1985

Development of quantitative structure-pharmacokinetic relationships.

Quantitative structure-activity relationships (QSAR) relating biological activity to physiochemical descriptors have been successfully used for a number of years. It is also long recognized that pharmacokinetic parameters may play an important and even determinant role in drug action. This prompted several researchers to focus attention to pharmacokinetic parameters as potential descriptors in quantitative drug design. A number of examples of quantitative structure-pharmacokinetic relationships (QSPR) have appeared in the literature. The present contribution reviews some developments in this field. In particular, a number of concepts and problems are critically discussed, rather than compilations of examples already published in recent reviews. Attention will be paid to the main processes of the pharmacokinetic or toxicokinetic phase in drug action, including absorption, distribution and elimination (biotransformation and excretion). It is clear that quantitative approaches are of considerable interest to toxicologists, since these methods may contribute to the development of real predictive toxicology.

Absorption↗
PubMed1984

Mechanisms of drug interactions with alcohol.

Pharmacokinetic and pharmacodynamic factors play important roles in alcohol-drug interactions. The combined acute administration of alcohol and many other drugs may result in potentially harmful interactions especially when central nervous system depressants are involved. Often the mechanisms responsible for an adverse alcohol-drug interaction include inhibition of biotransformation and enhancement of the central depressant effects. Long-term ingestion of alcohol can lead to hepatic enzyme induction and in many instances to enhanced biotransformation of numerous substances, usually resulting in reduced therapeutic effectiveness. Alcohol-drug interactions do not generally result in death, however, there is evidence for a contributory role of alcohol in many drug-related fatalities. The elderly and chronic drug users and abusers are especially at risk.

Animals↗
PubMed1983

Differential pharmacological responses to ethanol, pentobarbital and morphine in rats selectively bred for ethanol sensitivity.

The hypothermic and analgesic effects of ethanol, pentobarbital and morphine were examined in two lines of rats that had been selectively bred for their differential sensitivity to ethanol. Males and females of the least-affected (LA) line were observed to be less sensitive than their most-affected (MA) counterparts to hypothermia and analgesia induced by ethanol and morphine. By contrast, no differences were observed with respect to pentobarbital-induced hypothermia. At the dose used, pentobarbital had no significant analgesic effect in either animal line.

Analgesics↗
PubMed1982

Factors involved in the differential response to ethanol, barbital and pentobarbital in rats selectively bred for ethanol sensitivity.

Two lines of rats, 'least affected' (LA) and 'most affected' (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.

Animals↗
PubMed1982

Effect of naloxone on ethanol- and pentobarbital-induced narcosis.

Single or repeated subcutaneous administrations of naloxone in doses of up to 4 mg X kg-1 did not alter the time for onset or the duration of ethanol- or pentobarbital-induced narcosis in rats. An increase in the naloxone dosage to 50 mg X kg-1 s.c. resulted in a small reduction of ethanol-induced sleep duration. Repeated i.p. or i.v. administrations of much higher doses of naloxone (300-400 mg X kg-1 and 120-180 mg X kg-1, respectively) did produce significant reductions in ethanol-induced narcosis. However, similar naloxone doses, when administered alone, i.v., had marked convulsant effect. It appears that naloxone, in low doses, is not an effective antidote for narcosis caused by ethanol or pentobarbital at the ethanol and pentobarbital doses tested, whereas the antagonism of ethanol-induced sleep by high doses of naloxone may be due to the analeptic action of this drug.

Animals↗
PubMed1981

Different sites of action for morphine, ethanol, barbital and pentobarbital within the guinea-pig ileum longitudinal muscle/myenteric plexus preparation.

Morphine, ethanol, barbital and pentobarbital reversibly inhibited in a dose-dependent manner, the electrically evoked contractions of the guinea-pig ileum longitudinal muscle/myenteric plexus (LM/MP) preparation, in vitro. The ED50s for inhibition were 0.2 microM for morphine and 120, 8 and 0.3 mM for ethanol, barbital and pentobarbital respectively. To determine whether the site of inhibition was pre- or postjunctioal we studied the effects of graded concentrations of these drugs on the contractions evoked by exogenous acetylcholine (ACh). A correlation between the inhibition of the electrically and ACh-evoked muscle contractions suggests that morphine acts primarily prejunctionally while ethanol acts both pre-and postjunctionally. The inhibition by barbital and pentobarbital, however, can be accounted completely by a postjunctional depression. These results may explain our previous observation of cross-tolerance between morphine and ethanol in this preparation, and the lack of cross-tolerance between these drugs and barbital.

Acetylcholine↗