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At least 1,207 records · Page 67Linked to original sources
PubMed1989

A grease-gap method for studying the excitatory amino acid pharmacology of CA1 hippocampal pyramidal cells.

A grease-gap method for studying the pharmacology of CA1 hippocampal pyramidal cells was developed with use of rat hippocampal slices that included only area CA1 and the retrohippocampal area. These slices were transferred to a two-compartment superfusion chamber and the pyramidal cell bodies in area CA1 were separated from their axons in the subiculum with a grease barrier. The CA1 pyramidal cells were depolarized relative to their axons by superfusion with N-methyl-D-aspartate (NMDA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and L-glutamate. NMDA was unusually potent in the CA1-subiculum slice compared to other preparations. The NMDA receptor antagonists D(-)-2-amino-5-phosphonovalerate (D-AP5), phencyclidine and Mg2+ shifted the NMDA dose-response curve to the right in a parallel manner. Similarly, the quisqualate receptor antagonist pentobarbitone shifted the AMPA dose-response curve to the right. Schild plots for these antagonists had slopes insignificantly different from 1. These results are consistent with the presence of a substantial NMDA receptor reserve on CA1 pyramidal cells. They are also in line with the high density of excitatory amino acid receptors on CA1 hippocampal pyramidal cells and with the known pharmacological properties of these receptors. Grease-gap studies on the CA1-subiculum slice fill the need for a means of obtaining quantitative pharmacological data on CA1 pyramidal cells.

2-Amino-5-phosphonovalerate↗
PubMed1996

The Pharmacology of Nematode FMRFamide-related Peptides.

FMRFamide-related peptides (FaRPs) are the largest known family of invertebrate neuropeptides. Immunocytochemical screens of nematode tissues using antisera raised to these peptides have localized extensive FaRP-immunostaining to their nervous systems. Although 21 FaRPs have been isolated and sequenced from extracts of free-living and parasitic nematodes, available evidence indicates that other FaRPs await discovery. While our knowledge of the pharmacology of these native nematode neuropeptides is extremely limited, reports on their physiological activity in nematodes are ever increasing. All the nematode FaRPs examined so far have been found to have potent and varied actions on nematode neuromuscular activity. It is only through the extensive pharmacological and physiological assessment of the tissue, cell and receptor interactions of these peptidic messengers that an understanding of their activity on nematode neuromusculature will be possible. In this review, Aaron Maule and colleagues examine the current understanding of the pharmacology of nematode FaRPs.

Journal Article↗
PubMed1995

Molecular pharmacology of V1a vasopressin receptors.

1. Vasopressin, a mammalian neurohypophysial peptide hormone, has diverse physiological actions. 2. Pharmacological studies, using a range of mammalian tissues, have identified three subtypes of vasopressin receptor. 3. The V1a subtype of vasopressin receptor is widely distributed and mediates many central and peripheral actions of vasopressin. 4. The development of subtype-selective vasopressin analogues has provided valuable tools for pharmacological and physical studies of the V1a receptor protein. 5. Pharmacological differences indicate species heterogeneity in the characteristics of V1a receptors and in the expression of hepatic V1a receptors. 6. The cloning of neurohypophysial hormone receptor proteins allows structural and functional comparison of the V1a vasopressin receptors with other G-protein-coupled receptors.

Animals↗
PubMed1988

Benzodiazepine receptors in the human hippocampal formation: a pharmacological and quantitative autoradiographic study.

The pharmacological characteristics and anatomical distribution of benzodiazepine receptors in the human hippocampal formation were studied in seven cases aged 4-68 years. The pharmacology of the receptors was studied by computerized, non-linear least squares regression analysis of [3H]flunitrazepam displacement by flunitrazepam, CL218,872 and ethyl beta-carboline-3-carboxylate binding to membranes and the anatomical localization of these receptors was demonstrated using quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam. The pharmacological studies indicated that the human hippocampal formation contained equal numbers of benzodiazepine receptors with high affinity (Type I) and low affinity (Type II) for CL218,872 and ethyl beta-carboline-3-carboxylate. The autoradiograms demonstrated that the benzodiazepine receptors were distributed in a heterogeneous fashion throughout the major regions of the human hippocampal formation; the highest concentrations of receptors were present in the dentate gyrus (molecular layer) and field CA1 of Ammon's horn (strata pyramidale, oriens, lacunosum), with moderate concentrations in field CA2 of Ammon's horn (stratum pyramidale) and in regions of the subicular complex and entorhinal cortex, and with considerably lower densities in fields CA3 and CA4. Quantitative analyses of the autoradiograms showed that the regions containing the highest densities of receptors (molecular layer of dentate gyrus and the strata oriens, pyramidale and lacunosum of CA1) were enriched with Type 1 receptors whereas other regions of lower receptor densities were enriched with either Type I or Type II receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Pharmacology, distribution, cellular localization, and development of GABAB binding in rodent cerebellum.

Quantitative receptor autoradiography using [3H]GABA under selective conditions was used to characterize the pharmacology, distribution, cellular localization, and development of GABAB binding sites in rodent cerebellum. Pharmacologic analysis of [3H]GABA binding showed that drugs active at GABAB receptors displaced [3H]GABA with the following order of potency: 3-aminopropylphosphonous acid > CGP 35348 = 2-hydroxysaclofen > phaclofen. GTP-gamma-S and GDP-beta-S also diminished potently [3H]GABA binding in a dose-dependent manner. The pattern of [3H]GABA binding to GABAB binding sites was systematically mapped throughout the rat cerebellum. GABAB binding was greatest in the molecular layer and a pattern of parasagittal zonation was observed in the molecular layer of lobules VII-X in adult rats. The cellular localization of GABAB binding was investigated using lesion techniques. Neither methyl azoxymethanol lesions of cerebellar granule cells nor 3-acetylpyridine lesions of climbing fibers resulted in a decrease in [3H]GABA binding. Homozygote stumbler mutant mice, deficient in Purkinje cell dendrites, had a significant decrease in [3H]GABA binding in the molecular layer. These results suggest that the majority of cerebellar molecular layer GABAB binding sites detected by [3H]GABA autoradiography are located on Purkinje cell dendrites. Examination of [3H]GABA binding to GABAB binding sites during development revealed that binding in the molecular layer peaks between postnatal day 14 and postnatal day 28 and then decreases to adult levels. Transient expression of high levels of GABAB binding was observed in the deep cerebellar nuclei, peaking at postnatal day 3 and decreasing to adult levels by postnatal day 21. Our investigation of GABAB pharmacology yielded data in agreement with previously reported results. We have described a parasagittal pattern of GABAB binding in the cerebellar molecular layer and assigned the majority of cerebellar GABAB binding sites to Purkinje cell dendrites. Finally, development studies reveal transient peaks in GABAB binding in the cerebellar molecular layer and deep cerebellar nuclei.

Adenosine Triphosphate↗
PubMed1991

Pharmacologic erection with intracavernosal injection for men with sexual dysfunction following irradiation: a preliminary report.

Impotence is a possible consequence of treatment of pituitary adenomas and prostatic carcinomas. Following pituitary irradiation, the effect has been attributed to decreased gonadotrophins, while a variety of mechanisms, primarily vascular and neurogenic, have been proposed to explain the impotence following irradiation of prostatic carcinomas. Men with impotence of any etiology have been entered on a program to evaluate prospectively the efficacy of intracavernosal injection of vasoactive compounds in producing a satisfactory erection with pharmacologic means. Ten of these men had developed impotence following therapy for pituitary adenomas (2) or prostatic carcinomas (8). Test doses of 0.1 to 0.5 ml of a phentolamine (1 mg/ml) and papaverine (30 mg/ml) mixture were used; the dose was titrated to produce an erection deemed sufficient for vaginal penetration. All patients achieved a satisfactory response (i.e., tumescence and rigidity) lasting 10 minutes to 3 hours. Seven patients have continued in the pharmacologic erection program, with six patients functioning normally, and the remaining patient noting decreased tumescence after 18 months of treatment, but adequate erections are maintained with supplemental penile ring. Two patients have discontinued intracavernosal injections due to inconvenience, and one patient was lost to follow-up. Recent substitution of prostaglandin E1 (PGE1) has produced similar results and has replaced the phentolamine-papaverine combination. These preliminary results indicate that pharmacologic erection can be achieved in patients with impotence related to the treatment of pituitary and prostatic neoplasms and represents a reasonable alternative to implanted penile prostheses.

Adenoma↗
PubMed1984

Street pharmacology: uses of cocaine and heroin in the treatment of addiction.

This paper examines a unique finding from a larger research study of methadone maintenance treatment at four treatment programs in three Northeastern states. In looking at methods used by narcotics addicts to withdraw or detoxify from heroin, we found a small group of persons who had successfully detoxified from heroin addiction using a structured injection regimen of gradually decreasing amounts of heroin and gradually increasing amounts of cocaine. While this paper represents the case study of ten cases, the regimen was reported by others as part of 'street pharmacology.' It is a relatively uncommon regimen, reportedly due to the expense of the procedure and the problems associated with cocaine abuse. It is the pharmacological aspects of the procedure which warrant attention. All ten cases reported little or no withdrawal symptoms after the last injection containing small amounts of heroin. It was widely believed that cocaine interacts with heroin in a way which masks withdrawal during the detoxification process, providing a measure of physiological relief. Information from the addict world on that interaction provides clues as to the biochemical properties of drug interactions and may suggest areas for further clinical and pharmacological research.

Adult↗
PubMed1995

Pharmacological evaluation of dimethylheptyl analogs of delta 9-THC: reassessment of the putative three-point cannabinoid-receptor interaction.

The basic premise underlying the cannabinoid pharmacophore is that at least three functional groups are involved in the interaction between the ligand and the receptor and that these functional groups in delta 9-THC comprise (a) C11, (b) the phenolic hydroxyl, and (c) the side chain. In order to assess the relative importance of the C11 position and the side chain, a series of C11 substituted analogs were prepared which contained a dimethylheptyl side chain. Consistent with previous studies, incorporation of a dimethylheptyl side chain dramatically enhanced both pharmacological potency in mice and receptor affinity. Incorporation of a hydroxy at C11 along with this branched side chain resulted in an extremely potent cannabinoid with ED50S of 0.01, 0.04, 0.16 and 0.04 mumol/kg in depression of spontaneous activity, reduction in body temperature, antinociception, and immobility, respectively. This compound was also very potent as a discriminative stimulus in a drug discrimination procedure and exhibited an extended duration of action. Its high affinity for the cannabinoid receptor (Ki = 400 pM) was consistent with this pharmacological potency. Incorporation of an oxo rather than a hydroxy reduced potency somewhat, although this analog was much more potent than delta 9-THC in most behavioral assays. The most striking observation was that incorporation of a carboxylic acid to form 11-nor-delta 9-THC-DMH-9-carboxylic acid did not eliminate pharmacological activity. This analog was as potent as delta 9-THC. The improbability that all three of the functional groups are interacting in a similar fashion with the receptor provides further support that the C11 position is not an essential requirement for activity. On the other hand, it is possible that substituents in the C9 region are interacting somewhere within or near the same site, but differently.

Animals↗
PubMed1993

Research on pharmacologically active natural products at the Department of Pharmacognosy, Uppsala University.

Since 1954, research at the Department of Pharmacognosy at Uppsala University has been oriented towards modern natural products chemistry with emphasis on pharmacologically active compounds. Studies of plants used in the traditional medicine of different cultures have been of major interest. The research strategy is based on: inventory and identification of the plants used, demonstration of pharmacological activity of an extract of the plant, bioassay-guided fractionation, isolation and characterisation of the active compounds and studies of structure activity relationships. Plants from Africa, Asia, The Americas, The Pacific and Europe have been collected in collaboration with botanists and ethnobotanists. Investigations of these plants have resulted in the isolation, and chemical and pharmacological characterization of many different types of compounds. At present the work is focused on compounds with anti-inflammatory and immunomodulatory effects.

Africa↗
PubMed1995

Isolation of cholinergic active ingredients in aqueous extracts of Mareya micrantha using the longitudinal muscle of isolated guinea-pig ileum as a pharmacological activity marker.

In our attempt to isolate the pharmacologically active ingredients in the aqueous extracts of Mareya micrantha, we have selected the contractions of the longitudinal muscle of the isolated guinea-pig ileum preparation as a pharmacological marker to monitor retention of pharmacological activity during the chromatographic separation. The aqueous extracts of Mareya micrantha elicited concentration-dependent contractions of the preparation. The maximum response elicited by the aqueous extracts was 50% of the maximum response elicited by the maximum dose of acetylcholine (ACh), 10(-7) M. Mepenzolate (10(-8)-10(-5) M), a specific muscarinic receptor antagonist, similarly antagonized contractions elicited by the aqueous extracts suggesting that the cholinergic ingredient(s) in the extract are acting at the muscarinic receptors of the preparation. Fraction 2-4, which was separated from the aqueous extracts by Sephadex gel chromatography, dose-dependently elicited contractions of the preparation. The maximum response was 80% of the maximum response elicited by the maximum dose of ACh suggesting that separation has enhanced the cholinergic activity of the content in the extract.

Acetylcholine↗
PubMed1993

Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands.

We characterized the pharmacological profiles of the human mineralocorticoid and glucocorticoid receptor for 11 natural and synthetic steroids regarding binding pharmacology, intracellular localization of hormone-receptor complexes, and agonistic or antagonistic properties at the gene expression level. The sex steroid progesterone bound with an affinity (ki < 0.01 nM) even higher than that of aldosterone to the human mineralocorticoid receptor and effectively antagonized the effect of aldosterone via the human mineralocorticoid receptor in functional co-transfection assays. This indicates that progesterone has potent antimineralocorticoid properties, while its antiglucocorticoid effects were less pronounced. The partial agonistic activities of antihormones in this assay suggest a direct interaction of antihormone-receptor complexes with the response elements on the DNA. These results are supported by immunofluorescence studies, in which both unliganded human mineralocorticoid and glucocorticoid receptors were distributed throughout the cytoplasm and nucleus, whereas agonist- as well as antagonist-receptor complexes showed an exclusively nuclear localization. These results contribute to the understanding of antihormone pharmacology and increase our understanding of the role of human mineralocorticoid and glucocorticoid receptors in physiological processes during different endocrine states.

Aldosterone↗
PubMed1994

Pharmacology of antineoplastic agents in pregnancy.

The use of antineoplastic agents in pregnant women poses obvious risks to both the patient and the developing fetus, particularly during organogenesis. While the use of antineoplastics during pregnancy is often unavoidable, the physician may limit the risks by having a clear knowledge of the pharmacology and teratogenic potential of individual agents. Specific physiologic changes in the pregnant patient, such as enhanced renal excretion of drugs, increased or decreased hepatic function, altered gastrointestinal absorption and enterohepatic circulation, altered plasma protein binding, an increase in plasma volume (50%), and creation of a fluid filled 3rd compartment (amniotic fluid) for water soluble drugs may all significantly influence the pharmacology of antineoplastic agents. These physiological changes may effect the pregnant patients ability to absorb orally administered drugs, metabolize drugs to either active or inactive metabolites, and eliminate cytotoxically active drugs. A resulting reduction in concentration x time (C x T) for drug exposure to the maternal system may reduce the efficacy of the antineoplastic agents, while an increase in C x T may expose the patient and her fetus to undue toxicity. The timing of drug administration to gestational age is also a critical factor for some drugs. While many drugs result in adverse effects on the fetus regardless of gestational age, others appear to pose less of a threat if administered beyond the first trimester. This review addresses the pharmacology, pharmacokinetics and the teratogenic potential of individual antineoplastic agents that are commonly used in pregnant patients. The aim of this review is to help the physician select, on a patient specific basis, antineoplastic agents that avoid at least some of the fetal risk involved while maintaining efficacy in the treatment of the patient.

Abnormalities, Radiation-Induced↗
PubMed2005

A comprehensive ethical framework for responsibly designing and conducting pharmacologic research that involves pregnant women.

OBJECTIVE: We present and defend ethically justified guidelines for pharmacologic research that involves pregnant women. STUDY DESIGN: We explain the ethical concept of the fetus as a patient and identify its ethical implications for the design and conduct of pharmacologic research that is intended to benefit pregnant women. RESULTS: This concept justifies criteria for the initiation of early-phase clinical investigation, the initiation of controlled trials, the use of placebo control subjects, the stopping of randomized controlled trials, the determination of when an experimental intervention should be regarded as standard of care, and research that involves adolescents. The informed consent process should be shaped by the pregnant patient's obligation to take in to account her beneficence-based obligations to a fetal patient. Selection criteria should not be based on abortion preference. And, physicians are justified ethically in referring pregnant women to trials. CONCLUSION: The concept of the fetus as a patient plays an essential role in the ethically justified design and conduct of pharmacologic research in pregnant women.

Abortion, Induced↗
PubMed2004

The future of pharmacologic stress: selective A2A adenosine receptor agonists.

Adenosine and dipyridamole, the currently available vasodilators for myocardial perfusion imaging, produce hyperemic coronary flow by stimulating A(2A) adenosine receptors on arteriolar vascular smooth muscle cells. However, both vasodilators nonselectively activate A(1), A(2B), and A(3) adenosine receptors, which contributes to common undesirable effects. In the development of a novel pharmacologic stress agent, more selective agonism of the A(2A) receptor subtype would be desirable. Currently, 2 selective A(2A) adenosine receptor agonists are being evaluated in phase 3 studies as pharmacologic stress agents. The highly selective, potent, low-affinity A(2A) adenosine agonist regadenoson (also known as CVT-3146) holds significant potential as a pharmacologic stress agent, based on available results from experimental and clinical trials. Regadenoson produces maximal hyperemia quickly and maintains it for an optimal duration that is practical for radionuclide myocardial perfusion imaging. Regadenoson's simple rapid bolus administration and short duration of hyperemic effect point to an advantage of enhanced control for the clinician.

Adenosine A2 Receptor Agonists↗
PubMed2004

[Pharmacology and upper limb poststroke spasticity: a review. International Society of Prosthetics and Orthotics].

OBJECTIVES: The present study, conducted for the consensus conference "Orthotic management of stroke patients", organized by the International Society of Prosthetics and Orthotics, on September 2003, reviews the pharmacological, general, or local treatments available for post-stroke upper-limb spasticity. METHOD: A search of the international literature in the Medline and the Reedoc data banks for papers related to post-stroke upper-limb spasticity. Each paper was given a rating of A, B, or C (in term of quality) according to the instructions of the organization committee. RESULTS: General pharmacological treatments such as use of baclofen, tizanidine and dantrolene, regional treatments such as intrathecal baclofen, and local treatments with use of chemical neurolysis and alcohol or phenol are recommended for conditions described in papers with a grade of B. Neuromuscular blockade with botulinum toxin is recommended for conditions described in papers with a grade of A. DISCUSSION/CONCLUSION: Despite a satisfactory grade of recommendation, general pharmacological treatments are limited by adverse events and lack of evidence of functional benefit. Intrathecal baclofen should be discussed for upper-limb spasticity, but further studies are needed before its use can be recommended. The place of chemical neurolysis with use of alcohol or phenol should be evaluated with surgical neurotomy and botulinum toxin therapy. The use of botulinum toxin is the only treatment supported by scientific results, but many questions remain about the site of injection, how to improve efficacy and influence on neurological recovery.

Arm↗
PubMed2005

Effects of dietary and pharmacological manipulations on appetitive and consummatory aspects of feeding in non-human primates.

This study examined how pharmacological and behavioral manipulations affect appetitive and consummatory aspects of feeding of baboons. Baboons have access to food 24 h each day, but they must complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, i.e. a meal, where responding on another lever led to food delivery. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Decreasing session length, increased appetitive behavior and increased meal size. Limiting the number of meals to a single 90 min meal each day but increasing the number of food pellets the animals received increased the size of meal, but did not increase appetitive behavior. These findings suggest that time since the previous meal has a greater effect on appetitive behavior than the size of the previous meal. Amphetamine (AMPH), which increases dopamine, decreased food intake at doses that did not affect appetitive behavior, indicating that appetitive and consummatory aspects of eating can be pharmacologically differentiated. Increasing how frequently animals could earn food-related stimuli in the appetitive phase and food in the consummatory phase increased both appetitive and consumatory behavior. Under these conditions, AMPH nearly doubled appetitive behavior at doses that decreased food intake by nearly 50 percent. When animals had one meal, of self-determined duration, meal size increased without affecting appetitive behavior, further demonstrating that appetitive behavior can be independent of the size of the previous meal and not predictive of the size of the subsequent meal. Under these conditions, AMPH decreased food intake at doses that did not affect appetitive behavior. In contrast, dexfenfluramine (DFEN), which increases serotonin, decreased both appetitive and consumatory behavior. Thus, it is possible to independently manipulate the appetitive and consummatory aspects of eating using both pharmacological and behavioral interventions indicating that it may be possible to develop medications that selectively affect appetitive or consummatory aspects of eating.

Amphetamine↗
PubMed2006

[Pain in neonates: pharmacological treatment].

Pain causes numerous physiological changes in neonates. All invasive procedures induce undesirable stress responses; theses responses can, however, be eliminated or reduced by a judicious use of analgesia. Even though a large number of analgesics and sedatives are currently available, most of them have not been studied in the neonate. At present, a precise understanding of the pharmacological mechanisms of analgesics is difficult because many interactions still remain unknown in the term and premature neonate. This article describes the main analgesics and sedative agents used in the neonate: morphine, fentanyl, sufentanil, alfentanil, nalbuphine, ketamine, midazolam, propofol, acetaminophen, and Emla cream. After a review of the literature regarding these drugs, some practical advices and suggestions for the treatment of procedure-induced pain, and background sedation/analgesia for ventilated neonates are given. It is also stated in this article that the best way to soothe pain in neonates is to combine non pharmacological and pharmacological strategies. At the national level, written guidelines should be prepared in order to improve pain management in the neonate.

Analgesics, Non-Narcotic↗