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PubMed2001

5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle.

5-Hydroxytryptamine (5-HT) increases human heart rate and atrial contractile force and hastens atrial relaxation through 5-HT4 receptors. Moreover, 5-HT may be arrhythmogenic and give rise to atrial fibrillation. It is not clear which splice variant(s) of the 5-HT4 receptor is expressed and mediates these effects of 5-HT in the human heart. Previous studies have indicated different pharmacological properties of 5-HT4 receptors in human heart and mouse colliculi neurones, possibly due to expression of different splice variants. We therefore cloned the human 5-HT4(b) receptor and compared its pharmacological properties with those of the cloned human 5-HT4(a) receptor and searched for the corresponding mRNA in human tissues. The primary structures of the two human 5-HT4 receptor splice variants are identical except for divergent C-terminal tails of 28 and 29 amino acids in the 5-HT4(a) and 5-HT4(b) receptors, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that both variants were coexpressed in various tissues, including cardiac atrium and ventricle. Additional bands suggested the presence of more than two human 5-HT4 receptor splice variants. With cloned receptors stably expressed in HEK293 cells or transiently expressed in COS-7 cells, [3H]GR 113808 consistently showed slightly higher binding affinity to h5-HT4(b) than to h5-HT4(a) receptor (pKd 0.1-0.2 log units higher). Competition of agonists, partial agonists and antagonists for [3H]GR113808 binding revealed no significant differences between the two receptors. For 5-HT4 receptor agonists and antagonists, their potencies in stimulating or inhibiting, respectively, 5-HT-stimulated adenylyl cyclase activity correlated well with their binding affinities. Tropisetron and SB207710 showed partial agonist activity at high receptor expression levels for both isoforms. Cisapride and renzapride were both partial agonists at moderate receptor levels and full agonists at high receptor levels. Cisapride was more potent than renzapride while the converse was the case in human atrium, for which cisapride had lower affinity and agonist potency than at the recombinant receptors. The binding affinities and agonist potencies of ligands for both 5-HT4(a) and 5-HT4(b) receptors correlated with the corresponding affinities and potencies in human atrium. The agonist potency of SB207710 was around 10 times lower than its binding and blocking affinity for both splice variants, suggesting that activation of adenylyl cyclase and blockade of 5-HT responses are mediated through different conformational states. The similar pharmacological properties of the two human 5-HT4 receptor splice variants together with their expression in human atrium would be consistent with mediation of the cardiostimulant effects of 5-HT through both variants. However, the effects of cisapride appear either mediated through non-a and non-b splice variants of the 5-HT4 receptor or 5-HT4(a) and 5-HT4(b) receptor expression in human atrial cells alters somewhat their pharmacological profile through still unknown mechanisms.

Adenylyl Cyclases↗
PubMed2001

St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.

RATIONALE: St. John's wort (Hypericum perforatum) has recently gained popularity as an alternative treatment for mild to moderate depression. Given the current widespread use of this herbal remedy, it is important for medical professionals to understand the potential pharmacological pathways through which Hypericum may exert an antidepressant effect. OBJECTIVES: (1) To review the current pharmacological, toxicological, and clinical literature available on Hypericum, and (2) to provide a synthesis of this information into a form that may be easily used by health care providers. METHOD: A comprehensive review of the recent scientific literature (January 1990-March 2000) was performed using the following electronic databases and reference publications: MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all editions), European Scientific Cooperative on Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk Reference for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107) publications in the English language and three publications in German were included in the review. Collectively, the data suggest that therapeutic preparations of Hypericum extract appear to exert potentially significant pharmacological activity within several neurochemical systems believed to be implicated in the pathophysiology of depression. However, little information exists regarding the safety of Hypericum, including potential herb-drug interactions. CONCLUSIONS: Additional research on the pharmacological and biochemical activity of Hypericum and its several bioactive constituents is necessary to further elucidate the mode(s) of antidepressant action. Given what is currently known and unknown about the biological properties of Hypericum, those who choose to use this herb should be closely monitored by a physician.

Animals↗
PubMed2007

Pharmacology and surface electrostatics of the K channel outer pore vestibule.

In spite of a generally well-conserved outer vestibule and pore structure, there is considerable diversity in the pharmacology of K channels. We have investigated the role of specific outer vestibule charged residues in the pharmacology of K channels using tetraethylammonium (TEA) and a trivalent TEA analog, gallamine. Similar to Shaker K channels, gallamine block of Kv3.1 channels was more sensitive to solution ionic strength than was TEA block, a result consistent with a contribution from an electrostatic potential near the blocking site. In contrast, TEA block of another type of K channel (Kv2.1) was insensitive to solution ionic strength and these channels were resistant to block by gallamine. Neutralizing either of two lysine residues in the outer vestibule of these Kv2.1 channels conferred ionic strength sensitivity to TEA block. Kv2.1 channels with both lysines neutralized were sensitive to block by gallamine, and the ionic strength dependence of this block was greater than that for TEA. These results demonstrate that Kv3.1 (like Shaker) channels contain negatively charged residues in the outer vestibule of the pore that influence quaternary ammonium pharmacology. The presence of specific lysine residues in wild-type Kv2.1 channels produces an outer vestibule with little or no net charge, with important consequences for quaternary ammonium block. Neutralizing these key lysines results in a negatively charged vestibule with pharmacological properties approaching those of other types of K channels.

Action Potentials↗
PubMed2006

Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans.

PURPOSE: Response of myocardial blood flow (MBF) to sympathetic stimulation with cold is modulated by endothelium-related factors and is typically altered in the presence of coronary risk factors. Determinants of flow response to cold pressor testing (CPT) in normal volunteers at low risk for CAD remain less well defined, especially relative to baseline conditions such as hemodynamics and MBF, plasma substrate and lipid levels, and total pharmacologically stimulated vasodilator capacity. METHODS: In 50 normal volunteers (42+/-13 years; 31 women) without coronary risk factors, insulin resistance, or family history of diabetes/premature CAD, MBF was measured with (13)N-ammonia and PET at baseline, during CPT, and during pharmacologic hyperemia. RESULTS: Sympathetic stimulation with CPT raised heart rate and blood pressure and thus MBF (Delta MBF=0.23+/-0.09 ml/min/g). MBF response, defined in absolute flow units as the difference between CPT and baseline, was independent of age, gender, heart rate, and blood pressure and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid levels with the exception of an association with HDL cholesterol (rho=0.40, p=0.005) but depended on the change in RPP from rest (rho=0.33, p=0.019). Finally, changes in coronary vascular resistance in response to CPT were associated with changes in pharmacologic vasodilation (rho=0.56, p<0.0001). CONCLUSION: MBF response to sympathetic stimulation with cold (NO-mediated endothelium-dependent vasomotion), reflecting the functional state of the coronary endothelium, was independent of gender, age, and resting heart conditions. It was modulated by HDL cholesterol levels, even in healthy volunteers, and also related to pharmacologically stimulated vasodilator capacity at the coronary vascular resistance level.

Adult↗
PubMed2006

Pharmacologic vitreolysis with microplasmin increases vitreous diffusion coefficients.

BACKGROUND: Pharmacologic vitreolysis is a new approach to improve vitreo-retinal surgery and ultimately to liquefy and detach the vitreous from the retina to eliminate the contribution of the vitreous to retinopathy. The mechanism of action of the agents being developed for pharmacologic vitreolysis remains unclear. The effect of microplasmin on vitreous diffusion coefficients was investigated using the non-invasive technique of dynamic light scattering (DLS). METHODS: Vitreous diffusion coefficients in 18 intact porcine eyes were measured in vitro with dynamic light scattering (DLS). DLS was performed on all specimens at 37 degrees C 30 min after injections of human recombinant microplasmin at doses ranging from 0.125 to 0.8 mg, with 20-nm tracer nanospheres. RESULTS: DLS findings in untreated porcine vitreous were similar to the previously described findings in bovine and human vitreous. Microplasmin increased porcine vitreous diffusion coefficients in a dose-dependent manner (correlation coefficient, r=0.93), with an 85% increase after a 30-min exposure to the maximum dose. CONCLUSIONS: Pharmacologic vitreolysis with human recombinant microplasmin increases vitreous diffusion coefficients in vitro. The results of these studies have implications for the dosing, route of administration, duration of action and methods of determining efficacy in future studies of pharmacologic vitreolysis to enhance vitreo-retinal surgery, as well as the design of clinical trials to induce prophylactic posterior vitreous detachment.

Animals↗
PubMed2003

Marine pharmacology in 2000: marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antituberculosis, and antiviral activities; affecting the cardiovascular, immune, and nervous systems and other miscellaneous mechanisms of action.

During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors' 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories.

Anti-Bacterial Agents↗
PubMed2003

Pharmacologic radionuclide myocardial perfusion imaging.

Pharmacologic stress testing with myocardial perfusion imaging has enabled patients who cannot complete adequate exercise to undergo diagnostic and prognostic evaluation for coronary artery disease. Pharmacologic stress agents belong to two groups: vasodilators (such as adenosine and dipyridamole), and inotropes (such as dobutamine). All have similar sensitivity (89%-91%) and specificity (78%-86%) for the diagnosis of coronary disease. For risk stratification, the risk of future cardiac events is related to the extent and severity of perfusion abnormalities. Pharmacologic stress testing permits risk stratification as early as 1 to 4 days following an acute myocardial infarction, and is superior to exercise stress testing in this regard. Similarly, it identifies patients at high risk for perioperative cardiac events prior to noncardiac surgery. This review summarizes the current evidence available regarding the diagnostic and prognostic use of pharmacologic stress testing.

Coronary Artery Disease↗
PubMed2001

Pharmacologic treatment of fibromyalgia.

Fibromyalgia is a chronic syndrome characterized by widespread pain, unrefreshed sleep, disturbed mood, and fatigue. Until such time as we have a clearer understanding of the trigger and/or pathophysiologic mechanisms producing these symptoms, pharmacologic treatment should be aimed at individual symptoms. Such treatment should ideally be offered as part of a multidisciplinary treatment program using both pharmacologic and nonpharmacologic treatment modalities. Critical components of any successful fibromyalgia treatment program include addressing physical fitness, work and other functional activities, and mental health, in addition to symptom-specific therapies. The main symptoms that should be addressed include pain, sleep disturbances including restless leg syndrome, mood disturbances, and fatigue. Pharmacologic therapy should also be considered for syndromes commonly associated with fibromyalgia including irritable bowel syndrome, interstitial cystitis, migraine headaches, temporomandibular joint dysfunction, dysequilibrium including neurally mediated hypotension, sicca syndrome, and growth hormone deficiency. This article provides general guidelines in initiating a successful pharmacologic treatment program for fibromyalgia.

Analgesics↗
PubMed1990

Pharmacologic and pharmacokinetic characteristics of norgestimate and its metabolites.

Biotransformation, pharmacologic, and pharmacokinetic studies of norgestimate and its metabolites indicate that 17-deacetyl norgestimate, along with the parent drug, contributes to the biologic response. The postulated metabolic pathway, which is based on the identification of urinary products had indicated that three metabolites of norgestimate, 17-deacetyl norgestimate, 3-keto norgestimate, and levonorgestrel, might participate in the response. The pharmacologic evaluation of these metabolites demonstrates that only 17-deacetyl norgestimate has a pharmacologic profile consistent with that of norgestimate, and significant concentrations of this metabolite have been measured in the serum of women after the administration of norgestimate. These studies indicate that 17-deacetyl norgestimate contributes to the pharmacologic response to norgestimate.

Animals↗
PubMed1996

Pharmacological characterization of the cloned human 5-hydroxytryptamine transporter.

We performed an extensive pharmacological study of the 5-hydroxytryptamine (5-HT) transporter polypeptide cloned from human placenta. Transient expression of this 630 amino acid polypeptide in HeLa cells led to saturable 5-HT uptake activity (Km = 858 nM). This 5-HT uptake was blocked by selective 5-HT inhibitors, such as citalopram, litoxetine, sertraline, and indalpine, with Ki values in the low nanomolar range, and it exhibited a pharmacological profile similar to that found in rat brain. [3H]Citalopram binding to membrane preparations of the transfected cells occurred to a single class of high-affinity binding sites (Kd = 5.3 nM) and was potently inhibited by selective 5-HT uptake inhibitors. The pharmacological profile of [3H]citalopram binding to these transfected cells showed a good correlation with that of [3H]paroxetine binding to the rat cerebral cortical 5-HT transporter (r = 0.79). These data confirm that the full pharmacological characteristics of the 5-HT transport system are conferred by the expression of the 630 amino acid human placental 5-HT transporter polypeptide. [3H]Citalopram should, therefore, provide a useful probe for more insights at a molecular level into this cloned 5-HT transport system.

Antidepressive Agents, Tricyclic↗
PubMed1978

Pharmacological characterization of benzodiazepine receptors in the brain.

Receptors in rat brain membranes which specifically bind 3H-diazepam were characterized pharmacologically using reference substances representing several pharmacological classes of drugs. Of 28 benzodiazepines tested, several "classical" ones (diazepam, clonazepam, lorazepam, oxazepam, nitrazepam, flurazepam, bromazepam and chlorazepate) with known clinical efficacy, as well as three newer "triazolo" benzodiazepines (estazolam, U 35,005, U 31,957), one new "imidazolo" benzodiazepine, U 31,219, and one new 2-carbamoylmethylene-benzodiazepine, displaced 3H-diazepam binding at low concentrations (Ki=1--60 nM). For these benzodiazepines there was a stastically significant correlation between Ki values for displacement and ED50 (or MED) values in several pharmacological tests predictive of anxiolytic activity in man. More than 100 nonbenzodiazepines, representing 22 distinct pharmacological classes as well as 14 presumed neurotransmitters in the CNS, including 4 peptides, were much weaker as 3H-diazepam displacers (K2 greater than 0.1 nM). These results suggest that in vitro 3H-diazepam binding represents the physiologically relevant binding to hitherto unknown receptors in the CNS.

Animals↗
PubMed1985

Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin.

The pharmacological characteristics of the binding of [3H]8-OH-DPAT ([3H]8-hydroxy-2(di-n-propylamino)tetralin, [125I]CYP ((-)[125I]iodocyanopindolol) (in the presence of 30 microM (-)isoprenaline) and [3H]mesulergine to 5-HT1 recognition sites were studied in rat and pig brain membranes. [3H]8-OH-DPAT bound in rat and pig cortex to the 5-HT1A recognition site characterized by high affinity for 5-CT (5-carboxamido-tryptamine), 8-OH-DPAT, 5-HT (5-hydroxytryptamine, serotonin) and low affinity for pirenperone, ketanserin and mesulergine. [125I]CYP bound in rat but not in pig cortex to the 5-HT1B site which shows high affinity for (-)21-009 (4[3-ter-butyl-amino-2-hydroxy-propoxy]indol-2-carbonic acid isopropyl ester), (+/-)ICYP (3-I-cyanopindolol), 5-HT, RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridon-4-yl]1H-indole) and low affinity for 8-OH-DPAT, mesulergine and pirenperone. [3H]Mesulergine bound in pig choroid plexus and in rat cortex (besides binding to 5-HT2 sites in rat cortex) to the 5-HT1C recognition site characterized by high affinity for metergoline, mesulergine, 5-HT and methergine and low affinity for (-)21-009, ICYP, 8-OH-DPAT and spiroperidol. The pharmacological profile of 5-HT1A sites in rat and pig cortex appears to be identical; 5-HT1C sites in pig choroid plexus and rat cortex show no differences. In contrast, it was not possible to label 5-HT1B sites with [125I]CYP in pig brain membranes indicating that like 5-HT2 receptors, 5-HT1 recognition sites show species differences. The pharmacological profiles of the three 5-HT1 recognition sites are clearly different from one another. Furthermore, the pharmacological profile of each individual 5-HT1 recognition site is also different from that of the 5-HT2 receptors labelled with [3H]ketanserin in rat cortex membranes although some similarities exist between 5-HT2 and 5-HT1C sites. Finally, the beta-adrenoceptor antagonist (-)21-009 which has different affinities for 5-HT1A, 5-HT1B and 5-HT1C recognition sites, yielded triphasic competition curves for [3H]5-HT binding in rat cortex membranes providing evidence that [3H]5-HT labels three distinct 5-HT1 sites in these membranes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

2-[125I]iodomelatonin labels sites with identical pharmacological characteristics in chicken brain and chicken retina.

The binding and pharmacological characteristics of the melatonin site labeled by the radioligand 2-[125I]iodomelatonin in chicken brain membranes were determined and compared with those of the melatonin site of chicken retinal membranes. The specific binding of 2-[125I]iodomelatonin to chicken brain membranes was found to be stable, saturable, reversible and of high affinity. Scatchard analysis of the binding revealed an affinity constant (Kd) of 344 +/- 24 pM (n = 4) and a total number of binding sites (Bmax) of 57.6 +/- 10.1 fmol/mg protein (n = 4). The Kd value correspond closely with that found in kinetic studies (Kd = 407 pM) and that reported in chicken retinal membranes. Competition experiments were carried out with various compounds revealing the following order of pharmacological affinities: 6-chloromelatonin greater than or equal to 2-iodomelatonin greater than melatonin greater than 2-methyl-6,7-dichloromelatonin greater than 6-hydroxymelatonin greater than N-acetyl-5-hydroxytryptamine greater than luzindole greater than N-acetyl-5-methoxykynurenamine greater than 6-methoxymelatonin greater than N-acetyltryptamine greater than 5-methoxytryptamine greater than 5-hydroxytryptamine greater than 5-methoxy-N,N-dimethyltryptamine greater than 5-methoxytryptophol. This order of pharmacological affinities is identical to that found in chicken retinal membranes. Correlation between affinity constants for various melatonin receptor agonists and putative melatonin receptor antagonists obtained in chicken brain and retinal membranes yielded a correlation coefficient (r) of 0.966 (slope = 0.652, n = 14, P less than 0.01). We conclude that the high affinity site labeled by 2-[125I]iodomelatonin in chicken brain membranes has identical binding and pharmacological characteristics to the ML-1 melatonin receptor site previously described in chicken retinal membranes.

Animals↗
PubMed1992

Pharmacological characterization of a 5-HT receptor in locust nervous tissue.

A 5-HT receptor in the nervous tissue of the desert locust (Schistocerca gregaria Forsk.) was investigated, using [3H]LSD (lysergic acid diethylamide) as the radioligand. [3H]LSD labels in addition a putative dopamine receptor whose specific [3H]LSD binding nevertheless could easily be diminished by co-incubation with 1 microM dopamine. The binding site was characterized by a KD of 1.64 nM, and a maximal concentration of binding sites of 79.8 fmol/mg protein. Pharmacological investigation revealed a relatively low affinity for the putative natural agonist, serotonin (KI = 0.209 microM). In contrast to the high affinity of classical serotonergic antagonists (e.g. dihydroergotamine or (+)-butaclamol) substances with subtype specificity such as 8-OH-DPAT (8-hydroxyl-1-(N,N-dipropyl)-aminotetralin) or ketanserin have only moderate affinities. Quantitative comparison of the pharmacological data demonstrated that there is obviously no pharmacological homology with vertebrate 5-HT receptors characterized so far. The only receptors with a close pharmacological relationship to the 5-HT receptor of locusts are the 5-HTdro1 receptor expressed in Drosophila nervous tissue and a 5-HT receptor in snail nervous tissue which might be homologous to that of locusts. The 5-HT receptor investigated, was shown to be G-protein-coupled, as addition of stable GTP analogues or depletion of Mg2+ ions from the incubation medium led to agonist-specific lowering of the affinity.

Animals↗
PubMed1984

"Calcium antagonists": a class of drugs with a bright future. Part II. Determination of basic pharmacological properties.

This minireview discusses some simple pharmacological tests useful in detecting biological activity (screening), characterizing mechanisms of action and predicting possible therapeutic applications for calcium antagonists in general and calcium slow channel blockers in particular. In smooth muscle preparations these agents inhibit mechanical effects evoked by K+-depolarization which selectively opens voltage-operated calcium channels (VOC) to allow extracellular Ca++ into the cytosol. In contrast, any inhibition of receptor-mediated responses by calcium antagonists appears to depend on the transduction system and the specific cellular mechanism (e.g. VOC opening consequent to partial depolarization) activated by the receptor and, evidently, on ancillary pharmacological properties of the studied compound. For instance, whereas calcium slow channel blockers antagonize contractions produced by norepinephrine and K+-depolarization in the rat isolated portal vein, they inhibit effectively only the latter response in the rabbit aorta. This apparent discrepancy may be accounted for by the different pool of Ca++ mobilized in the two tissues by norepinephrine. Agents (e.g. diphenylalkylamines, calmodulin blockers) that impair the interaction of Ca++ with intracellular proteins produce effects which are less specific than those of slow channel blockers. Currently, the pharmacological profile of calcium antagonists can be appropriately defined by studying their effects on radioligand (dihydropyridine) binding, radioactive calcium movements through biological membranes, electrophysiological parameters in cardiac and vascular smooth muscle and on various in vivo cardiovascular preparations. Together, these approaches allow a functional classification of new calcium antagonists in relation to already known compounds and some hypotheses on their potential clinical applications. Finally, desirable pharmacokinetics and pharmacological properties for novel calcium antagonists are mentioned. This point will be further explored in the forthcoming minireview which will deal with the clinical applications of calcium antagonists.

Animals↗
PubMed1986

Relationships of brain and plasma levels of quazepam, flurazepam, and their metabolites with pharmacological activity in mice.

The relationships between the pharmacological activities of quazepam and flurazepam and the concentrations of each drug and its major active metabolites in brain and plasma following single oral doses of either drug to mice were investigated. At various time points after either quazepam or flurazepam administration, pharmacological activity was measured by the inhibition of electroconvulsive shock (ECS)-induced seizures. After quazepam, the plasma and brain samples obtained at the same time points were assayed for concentrations of quazepam, 2-oxoquazepam and N-desalkyl-2-oxoquazepam by specific GLC methods. After flurazepam, the plasma and brain samples were assayed for flurazepam, hydroxyethyl-flurazepam, and N-desalkyl-2-oxoquazepam, also by specific GLC methods. The results showed that both quazepam and flurazepam were rapidly metabolized and that parent drugs and metabolites were rapidly distributed to the brain. The brain levels of all the benzodiazepines analyzed in this study paralleled plasma levels. After quazepam, pharmacological activity most closely paralleled the combined brain concentrations of quazepam and 2-oxoquazepam rather than N-desalkyl-2-oxoquazepam levels. In contrast, following the flurazepam dose, activity most closely paralleled N-desalkyl-flurazepam concentrations. From these data, it can be concluded quazepam is distinctly different from flurazepam, and that, in the presence of quazepam and 2-oxoquazepam, N-desalkyl-2-oxoquazepam does not contribute extensively to the observed pharmacological activity.

Animals↗
PubMed1994

Pharmacological versus sensory factors in the satiation of chocolate craving.

This is the first experimental study directed at differentiating between physiological or sensory accounts of the satiation of nondrug cravings, using chocolate craving, the most common craving in North America. At the onset of craving, chocolate cravers consumed a chocolate bar, the caloric equivalent in "white chocolate" (containing none of the pharmacological components of chocolate), the pharmacological equivalent in cocoa capsules, placebo, and no treatment conditions had virtually no effect. White chocolate produced partial abatement, unchanged by the addition of all the pharmacological factors in cocoa. This result indicates no role for pharmacological effects in the satisfaction of chocolate craving. It also suggests a role for aroma independent of sweetness, texture, and calories.

Adult↗
PubMed1979

Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors.

Brain-specific binding sites have been isolated on synaptosomal membrane fragments which recognize pharmacologically active benzodiazepines (BDZ's) and triazolopyridazines (TPZ's). While early evidence indicated the existence of a single homogeneous class of BDZ binding sites, more recent biological and pharmacological studies support the notion of BDZ receptor multiplicity. We now propose that two biochemically distinct BDZ receptors exist in brain which are responsible for the mediation of different pharmacological activities. Type I BDZ receptors display a high affinity for both BDZ's and TPZ's, are not coupled to GABA receptors or to chloride ionophores, and are the sites which mediate anxiolytic actions. Type II BDZ receptors display a high affinity for BDZ's, display a low affinity for TPZ's, are coupled to GABA receptors and/or chloride ionophores, and are the sites which mediate pharmacological effects other than anxiolytic activity.

Animals↗