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  • 1
    Electronic Resource
    Electronic Resource
    Reduction in phenytoin clearance caused by cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 135-137 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; drug interactions ; cimetidine ; inhibition of metabolism ; disposition kinetics ; mixed function oxidases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine on the disposition kinetics of phenytoin was investigated in 7 healthy volunteers. Each subject received a single intravenous dose of phenytoin on two occasions, in the control state, and during concurrent treatment with cimetidine 1200 mg/day for 6 days. A slight but statistically significant decrease both in the rate of elimination and total body clearance of phenytoin was observed during the administration of cimetidine. The effect is probably due to inhibition of metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544030
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  • 2
    Electronic Resource
    Electronic Resource
    The pharmacological treatment of acute colonic pseudo-obstruction (2001)
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 15 (2001), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Acute colonic pseudo-obstruction (Ogilvie’s syndrome) can be defined as a clinical condition with symptoms, signs and radiological appearance of acute large bowel obstruction unrelated to any mechanical cause. Recent reports of the efficacy of cholinesterase inhibitors in relieving acute colonic pseudo-obstruction have fuelled interest in the pharmacological treatment of this condition. The aim of the present review is to outline current perspectives in the pharmacological treatment of patients with acute colonic pseudo-obstruction.The best documented pharmacological treatment of Ogilvie’s syndrome is intravenous neostigmine (2–2.5 mg), which leads to quick decompression in a significant proportion of patients after a single infusion. However, the search for new colokinetic agents for the treatment of lower gut motor disorders has made available a number of drugs that may also be therapeutic options for Ogilvie’s syndrome. Among these agents, the potential of 5-hydroxytryptamine-4 receptor agonists and motilin receptor agonists is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.2001.01088.x
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  • 3
    Electronic Resource
    Electronic Resource
    Clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 19 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood–brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood–brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood–brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.01867.x
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  • 4
    Electronic Resource
    Electronic Resource
    Changes in sensitivity to the inhibitory effects of adrenergic agonists on intestinal motor activity after chronic sympathetic denervation (1984)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 325 (1984), S. 145-152 
    Details
    ISSN: 1432-1912
    Keywords: Peristaltic reflex ; Intestinal motility ; Sympathetic denervation ; Supersensitivity ; Adrenoceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon. 2. The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine 〉 noradrenaline 〉 methoxamine 〉 isoprenaline for the inhibition of peristalsis and isoprenaline 〉 noradrenaline 〉 methoxamine 〉 clonidine for the relaxation of circular muscle. 3. Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both α and β receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release. 4. Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs. 5. Our results are consistent with a main role played by β receptors in the relaxation of circular smooth muscle and with a selective involvement of α2 receptors in peristalsis inhibition. The pattern of sensitivity changes is consistent with a high degree of physiological modulation by sympathetic supply both on the smooth muscle and on the intramural nervous structures. Both pre- and postjunctional mechanisms could be responsible for the development of supersensitivity, but the former seem to operate only at interneuronal synapses. The opposite sensitivity changes observed for noradrenaline and clonidine suggest a different effect of two agonists at the presynaptic level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00506194
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  • 5
    Electronic Resource
    Electronic Resource
    Involvement of substance P in the excitatory action of GABAA agonists on cholinergic neurons in the guinea-pig ileum (1987)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 335 (1987), S. 629-635 
    Details
    ISSN: 1432-1912
    Keywords: GABAA agonists ; Substance P ; Cholinergic neurons ; Guinea-pig ileum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The possible involvement of substance P (SP) in cholinergic contractions induced by GABAA agonists in the guinea-pig ileum was further investigated. 2. Responses evoked by 3-aminopropane sulphonic acid (3-APS) or muscimol consisted of a rapid phasic contraction followed in 70% of preparations by a tonic contraction, usually smaller in amplitude but considerably longer in duration. Phasic and tonic components were sensitive to bicuculline, neurogenic (cholinergic) in nature and susceptible to desensitization. 3. Capsaicin (0.2 μM) pretreatment and SP receptor desensitization caused by 3 different priming SP concentrations (10 nM, 30 nM, 100 nM), depressed both components of the 3-APS-induced response, the magnitude of antagonism being greater for tonic contractions. Similar findings were obtained by using 10 μM (d-Pro4, d-Trp7,9)SP-(4–11), even though the degree of antagonism caused by this SP antagonist was consistently lower. 4. These results indicate that depression of SP receptor function achieved by three different procedures decreases cholinergic contractile responses to GABAA agonists in the guinea-pig ileum. This provides further support for the hypothesis that GABAA receptor activation evokes both direct and indirect stimulation of enteric cholinergic neurons and that SP and/or a related peptide play an important role in mediating the indirect component of the cholinergic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00166979
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  • 6
    Electronic Resource
    Electronic Resource
    A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle (1997)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 750-755 
    Details
    ISSN: 1432-1912
    Keywords: Key words Human urinary bladder ; Detrusor strips ; Neuromuscular cholinergic transmission ; Adenosine triphosphate ; P2-purinoceptors ; Suramin ; PPADS ; ƒω-Conotoxin GVIA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1–50Hz for 5s at 1min intervals, 0.1ms pulse width, 60V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10μM). Tetrodotoxin (TTX: 1μM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (ω-CTX: 0.1μM). The atropine-resistant contractions were unaffected by the P2-purinoceptor antagonists suramin (300μM) and PPADS (30μM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10μM–1mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300μM) and PPADS (3, 10, 30μM) was insurmountable, with apparent ‘pA2’ values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P2-purinoceptors on the effector cells. The TTX- and ω-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na+- and N-type Ca2+-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005114
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacological studies of the rabbit and human renal pelvis (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 285 (1974), S. 209-222 
    Details
    ISSN: 1432-1912
    Keywords: Renal Pelvis Smooth Muscle ; Sympathomimetic Amines ; Transmural and Periarterial Stimulation ; α-adrenoceptors ; Adrenergic Blocking Agents ; Fluorescence Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of the isolated rabbit and human renal pelvis to drugs and to electrical stimulation have been investigated. Regular spontaneous changes in tension occur in the circular smooth muscle, which in the rabbit are synchronous with electrical waves. The responses to electrical stimulation seem to be due to the release of catecholamines from adrenergic nerves. Such nerves have been observed by means of a fluorescence technique. The cholinergic system appears functionally unimportant. The adrenergic responses in human and rabbit seem to be mediated exclusively by α-adrenoceptors. The denervated rabbit organ shows hypersensitivity, mainly to low concentrations of adrenaline. The failure of uptake inhibitors to potentiate the responses to noradrenaline seems in favour of postsynaptic hypersensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498991
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of pentazocine on the intestine and biliary tract of the rabbit in vitro (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 299 (1977), S. 207-210 
    Details
    ISSN: 1432-1912
    Keywords: Pentazocine ; Ileum ; Colon ; Bile duct ; Extracellular electrical activity ; Acetylcholine release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pentazocine impairs peristaltic activity and relaxes longitudinal muscle in the colon and in the ileum. The circular coat is excited in the colon, while in the ileum pentazocine exhibits both excitatory and inhibitory effects depending on the concentration employed. Pentazocine does not exert a spasmogenic effect in the smooth muscle of terminal bile duct but instead reduces the electrically-induced contraction. The effect of pentazocine does not seem to involve endogenous acetylcholine or catecholamine release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500312
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  • 9
    Electronic Resource
    Electronic Resource
    5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum (1983)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 324 (1983), S. 180-184 
    Details
    ISSN: 1432-1912
    Keywords: GABA ; 5-Hydroxytryptamine ; Guinea-pig ileum ; Desensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. GABA (3–100 μM) and 5-HT (0.03–30 μM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. 2. The contractile response to GABA was antagonized by hyoscine (2.2 μM), TTX (0.7 μM), bicuculline (3 μM), furosemide (25 μM) and desensitization to GABA itself, while hexamethonium (20 μM) and methysergide (20 μM) were without effect. 3. The contractile response to 5-HT was antagonized by hyoscine (2.2 μM), TTX (0.7 μM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 μM), hexamethonium (20 μM), furosemide (25 μM) and methysergide (20 μM). 4. A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 μM) concentrations of GABA. 5. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00503891
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  • 10
    Electronic Resource
    Electronic Resource
    Endomorphin-1 and endomorphin-2 activate µ-opioid receptors in myenteric neurons of the guinea-pig small intestine (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 358 (1998), S. 686-689 
    Details
    ISSN: 1432-1912
    Keywords: Key words Endomorphin-1 ; Endomorphin-2 ; µ-Opioid receptors ; Opioid receptor antagonists ; Longitudinal muscle-myenteric plexus preparation ; Guinea-pig ileum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central µ-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM–1 µM) inhibited (–log EC50 values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective µ-opioid receptor antagonist, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), caused a concentration-dependent (30 nM–1 µM), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA 2 values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective δ-receptor antagonist) or 30 nM nor-binaltorphimine (a selective κ-receptor antagonist). These results demonstrate that endomorphins selectively activate µ-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005313
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