Disposition of the opioid antagonist, nalmefene, in rat and dog.

1. The disposition of nalmefene in rat and dog was studied using in vitro and in vivo methodology. In vitro metabolite profiles were obtained following incubation of nalmefene with liver microsomes and biological fluids were assayed to profile in vivo metabolites.

Stability of Revex, nalmefene hydrochloride injection.

The stability of Revex, nalmefene hydrochloride injection, has been studied at several temperatures for periods up to 36 months. The data were obtained using a HPLC method for the potency determination, and for the level of the sole degradation product (2,2'-bisnalmefene). These methods were found to be characterized by excellent precision, linearity, and accuracy over the analyte concentration ranges established.

An analysis of social and psychological characteristics of women volunteering to become oocyte donors.

Objectives: To design a recruitment program and analysis to determine social and psychological characteristics of women who volunteer to be oocyte donors; to evaluate consistency between clinical interviews and psychological testing; and to determine whether socially and psychologically normal women tend to volunteer.

Participants: Over a 2-year period 95 women were recruited from a middle-class population surrounding the medical center. Candidates were evaluated on the basis of clinical interviews and performance on the Minnesota Multiphasic Personality Inventory.

D-amino acid and alanine scans of the bioactive portion of porcine motilin.

A recent systematic study of porcine motilin fragments has clearly shown that biological activity resides in the amino-terminal end. The amino-terminal tetradecapeptide retains more than 90% of the potency of the full molecule. We now examined the effect of replacement of residues 1 through 11 by either their D-isomer or by alanine in [Leu13]pMOT(1-14).

Synthesis and in vitro evaluation of [Leu13]porcine motilin fragments.

Several peptide fragments representing N-terminal, C-terminal, and internal sequences of [Leu13]porcine motilin ([Leu13]pMOT) were synthesized using Fmoc solid phase methodology. Peptides were assayed for motilin receptor binding activity in a rabbit antrum smooth muscle preparation and for stimulation of contractile activity in segments of rabbit duodenum. In vitro activity was directly correlated with motilin receptor binding affinity for all [Leu13]pMOT fragments examined.

Capillary zone electrophoresis studies of motilin peptides. Effects of charge, hydrophobicity, secondary structure and length.

Motilin is a gut hormone, which is involved in gastrointestinal motility. Capillary electrophoresis studies were made on 24 peptides that are N-terminal, C-terminal or internal fragments of motilin. The isoelectric point, total charge and hydrophobicity were calculated for all of the peptides.

A survey of public attitudes toward oocyte donation between sisters.

Oocyte donation offers the possibility of pregnancy for many patients with premature ovarian failure (POF) and recently a number of patients have been requesting egg donation by a sister. While patients anxious to achieve a pregnancy are favourably disposed toward egg donation, the existence of favourable attitudes in others, and thus the amount of social support such patients will receive, depends upon the wider social environment. A survey of public opinion was conducted utilizing a random sample of 501 adults in Orange County, CA in an attempt to identify demographic correlates of attitudes.

Metaphit inhibits dopamine transport and binding of [3H]methylphenidate, a proposed marker for the dopamine transport complex.

Metaphit, an acylating derivative of phencyclidine, was shown to interact with components of the dopamine nerve terminal in rat striatal tissue. This compound, previously demonstrated to be an irreversible inhibitor at the phencyclidine receptor, was shown in these experiments to irreversibly inhibit synaptosomal [3H]dopamine uptake. It also inhibited binding of [3H]methylphenidate to its recognition site, which is thought to be a subunit of the dopamine transporter.

Synthetic peptide analogues differentially alter the binding affinities of cyclic nucleotide dependent protein kinases for nucleotide substrates.

Analogues of a synthetic heptapeptide substrate corresponding to the sequence around a phosphorylation site in histone H2B [Glass, D. B. & Krebs, E.

Phencyclidine (PCP)-like inhibition of N-methyl-D-aspartate-evoked striatal acetylcholine release, H-TCP binding and synaptosomal dopamine uptake by metaphit, a proposed PCP receptor acylator.

The phencyclidine (PCP) receptor acylator, metaphit, has been reported to act as a PCP antagonist. Recent electrophysiological and behavioral assessments of metaphit action have revealed, however, that this compound can also act as a PCP-like agonist. The present study examined the effects of metaphit on the inhibition of N-methyl-D-aspartate (NMDA)-induced 3H-acetylcholine (ACh) release, 3H-TCP binding and synaptosomal 3H-dopamine (DA) uptake in the rat striatum.

Chronic morphine upregulates a mu-opiate binding site labeled by [3H]cycloFOXY: a novel opiate antagonist suitable for positron emission tomography.

CycloFOXY (17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta- fluoromorphinan) is a novel opiate antagonist synthesized as a ligand suitable for in vivo visualization of opiate receptors using positron emission transaxial tomography. In this paper we report that [3H]cycloFOXY labels two distinct opiate binding sites in rat brain membranes, tentatively identified as mu and kappa. Furthermore, chronic administration of morphine results in a selective up-regulation of the mu binding site.

[3H]cyclofoxy, a ligand suitable for positron emission tomography, labels mu and kappa opioid receptors.

The autoradiographic distribution of [3H]cyclofoxy (6-deoxy-6 beta-fluoronaltrexone) after in vivo administration or in vitro incubation suggests that it labels mu and kappa opioid receptors. In the rat, the pattern of [3H]cyclofoxy binding is similar to the distribution of mu receptors, however labeling is also present in the neural lobe of the pituitary, the central nucleus of the amygdala and the hypothalamus, areas where kappa receptors outnumber mu receptors. In the guinea pig, [3H]cyclofoxy binding sites are dense in the deep layers of the cortex, an area enriched in kappa receptors.

Enantiomeric and diastereomeric dioxadrols: behavioral, biochemical and chemical determination of the configuration necessary for phencyclidine-like properties.

Dioxadrol exists in four isomeric forms. alpha-(+)-Dioxadrol (dexoxadrol) showed phencyclidine (PCP)-like activity in rhesus monkeys trained to discriminate s.c.

Metaphit irreversibly inhibits [3H]threo-(+/-)-methylphenidate binding to rat striatal tissue.

Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine), a derivative of phencyclidine that contains an isothiocyanate group on the meta position of the aromatic ring, resembles its parent compound (phencyclidine) in its ability to inhibit the binding of the stimulant drug [3H]threo-(+/-)-methylphenidate to crude synaptosomal membranes from rat striatal tissue (IC50 = 1.4 and 6.2 microM for phencyclidine and Metaphit, respectively).

Probes for narcotic receptor mediated phenomena. 13. Potential irreversible narcotic antagonist-based ligands derived from 6,14-endo-ethenotetrahydronororipavine with 7-(methoxyfumaroyl)amino, (bromoacetyl)amino, or isothiocyanate electrophiles: chemistry, biochemistry, and pharmacology.

N-Allyl-, N-(cyclopropylmethyl)-, and N-propyl-endo-ethenotetrahydronororipavines (N-substituted 6,14-endo-etheno-4,5-epoxy-3-hydroxy-6-methoxymorphinans) were synthesized with potential acylating or alkylating moieties at the C-7 position (isothiocyanato, (bromoacetyl)amino, and (methoxyfumaroyl)amino) and examined in vivo for their narcotic agonist and antagonist activities and for their ability to interact with opioid receptors in vitro. The N-(cyclopropylmethyl)-substituted compounds were found to have the highest affinity for opioid receptors among these N-substituted compounds, although all of them were found to be reasonably potent narcotic antagonists in the mouse tail flick vs. morphine assay.

Electrophysiological interactions of isomers of cyclazocine with the phencyclidine antagonist metaphit in rat cerebellar Purkinje neurons.

Metaphit, 1-(1-(3-isothiocyanatophenyl) cyclohexyl) piperidine, an analog of phencyclidine (PCP) has been shown previously to selectively block PCP receptors and to irreversibly antagonize the depressant effect of PCP in cerebellum. In this study, we examined the electrophysiological interactions of metaphit and naloxone with stereoisomers of cyclazocine, an agent known to have analgesic and psychotomimetic activity in behavioral studies, effects that have been ascribed to opiate and PCP receptor activity. A dose-dependent and reversible slowing of Purkinje neuron discharge was seen with local application of (+)- or (-)-cyclazocine.

Metaphit, an acylating ligand for phencyclidine receptors: characterization of in vivo actions in the rat.

Metaphit, which acylates phencyclidine (PCP) receptors in vitro, was shown to acylate PCP receptors and antagonize the behavioral and electrophysiological effects of PCP in vivo. Metaphit (2 mumol/rat) administered i.c.

Metaphit, a receptor acylator, inactivates cocaine binding sites in striatum and antagonizes cocaine-induced locomotor stimulation in rodents.

The PCP analog metaphit, a proposed PCP receptor acylator, produced a concentration-dependent loss of the number of high-affinity [3H]cocaine binding sites in rodent striatum. In addition, 24 h after administration of metaphit, a dose of 25 mg/kg of cocaine was not effective in stimulating locomotor behavior of rodents. The results suggest that metaphit antagonizes cocaine-induced locomotor stimulation by acylating cocaine binding sites on dopaminergic nerve terminals.

Is Metaphit a phencyclidine antagonist? Studies with ketamine, phencyclidine and N-methylaspartate.

The dissociative anaesthetics, phencyclidine and ketamine, block excitation of central neurones by N-methylaspartate. Using the technique of microelectrophoresis on rat spinal neurones in vivo Metaphit, a phencyclidine receptor acylating agent, was tested to see whether it would antagonise this effect of dissociative anaesthetics. The predominant effect of Metaphit was, however, to reduce N-methylaspartate induced excitation.

Interactions of phencyclidine with hippocampal circuitry: evidence for neuronal heterogeneity.

The discovery of phencyclidine (PCP) receptors has stimulated the search for specific PCP antagonists. A direct product of this research is metaphit, an irreversible PCP ligand, which has recently been synthesized. In this study we examined the effects of metaphit on the responses of hippocampal neurons to PCP.

Metaphit, a proposed phencyclidine receptor acylator: phencyclidine-like behavioral effects and evidence of absence of antagonist activity in pigeons and in rhesus monkeys.

Metaphit, a derivative of phencyclidine (PCP), binds irreversibly to PCP sites and appears to act as an antagonist of PCP under some conditions and as a PCP-like agonist under other conditions. To describe further these conditions, the authors investigated the behavioral effects of metaphit by using different routes of administration, behavioral procedures and species. In pigeons, metaphit induced PCP-like catalepsy after i.

Antagonism of phencyclidine action by metaphit in rat cerebellar Purkinje neurons: an electrophysiological study.

Metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]piperidine), a derivative of the psychotomimetic drug phencyclidine (PCP), is postulated to bind irreversibly to PCP receptors. We examined here the electrophysiological interactions of metaphit with PCP in rat cerebellar cortex, since a specific effect of PCP on cerebellar neuronal circuitry has been shown. Metaphit, applied locally to Purkinje neurons by micropressure ejection through multibarreled micropipettes, has a reversible depressant action lasting for 5-20 min.