PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Piperoxan”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

The effects of piperoxan on uptake of noradrenaline and overflow of transmitter in the isolated blood perfused spleen of the cat.

1 The competitive alpha-adrenoceptor blocking agent, piperoxan, in concentrations up to 2 x 10(-4) M, produced large dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz. 2 At concentrations greater than 2 x 10(-4) M, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose-dependent decrease in transmitter overflow. 3 Phenoxybenzamine (10(-4) M) and desmethylimipramine (3 x 10(-5) M) produced further increases in transmitter overflow when added after piperoxan. 4 Piperoxan (5.8 to 6.6 x 10(-6) M) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of (3H)-(--)-noradrenaline, indicating that the drug does not inhibit uptake of the amine. 5 Piperoxan produced dose-dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 microgram of (--)-noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 x 10(-6) M piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation. 6 In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose-response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens.

Animals↗
PubMed1978

Effect of piperoxane on serum prolactin: possible role of epinephrine-mediated synapses in the inhibition of prolactin secretion.

Intravenous administration of 2,5 mg/kg piperoxane produced a rapid and significant increase in serum PRL concentrations in four non-human primates. This PRL increase was maximal 15 min after piperoxane infusion and significant, when compared with baseline levels, in the +15, +30, +45, +60, and +90-min samples. The iv administration of 5 mg/kg piperoxane also produced a rapid and significant increase, whereas saline 0.5 mg/kg or 1.0 mg/kg, did not change serum PRL levels. The iv administration of 10 microgram/kg clonidine, but not saline, produced a rapid and significant reduction in serum PRL levels. PRL levels were significantly reduced +15, +30, and +60 min after the clonidine infusion. Pretreatment with a bolus of 10 microgram/kg clonidine at -15 min caused a significant attenuation of the piperoxane-induced elevation in serum PRL in two monkeys. These data support the hypothesis that alpha-adrenergic receptors are involved in the inhibition of PRL secretion. These data are compatible with noradrenergic or adrenergic mechanisms which remain to be defined.

Animals↗
PubMed1977

Presynaptic alpha-adenoceptors: the depression of self-stimulation by clonidine and its restoration by piperoxane but not by phentolamine or phenoxybenzamine.

Depression of self-stimulation by clonidine has been ascribed to continuous direct stimulation of alpha-adrenoceptors with consequent disruption of reinforcement signals thought to be conveyed by noradrenergic pathways. This suggestion was tested by administration of alpha-receptor blocking agents (piperoxane, phentolamine and phenoxybenzamine, PBZ) differing in their affinity for pre- and post-synaptic receptor sites. Piperoxane in low doses (0.55-5.0 mg/kg) previously reported to cause specific blockade of pre-synaptic receptors implicated in negative feedback circuits, caused a significant increase in self-stimulation rate and strongly antagonized the depression of self-stimulation by clonidine (0.15 mg/kg). A larger dose of piperoxane (45 mg/kg) and graded doses of phentolamine and PBZ, affecting both pre- and post-synaptic receptors, depressed self-stimulation, and did not antagonize clonidine-induced depression of self-stimulation. It is concluded that depression of self-stimulation by clonidine may depend on clonidine-induced inhibition of NA release exerted via presynaptic receptors, and that the effect of clonidine is not necessarily evidence that noncontingent adrenergic stimulation disrupts reinforcement.

Animals↗
PubMed1978

Piperoxane reduces the effects of clonidine on aggression in mice and on noradrenaline dependent hypermotility in rats.

Aggression in isolated male mice and hypermotility in rats produced by the noradrenaline releaser H 77/77 were studied after the s.c. administration of the alpha-adrenergic agonist clonidine and the alpha-antagonist piperoxane. Clonidine 0.005--0.5 mg/kg inhibited both behaviours while piperoxane showed a weak and short-lasting antiaggressive effect and no H 77/77 antagonism. Inactive doses of piperoxane reduced the inhibitory effects of clonidine. The results indicate that isolation-induced aggression in mice and H 77/77-induced hypermotility in rats are behavioural signs related to the availability of noradrenaline at the receptor.

Aggression↗
PubMed1978

Effects of alpha-agonists on circulatory responses to somatic afferent nerve stimulation.

The effect of intracisternal (i.c.m.) injection of clonidine, noradrenaline, and piperoxane on the pressor response to electrical stimulation of a peripheral somatic afferent nerve was investigated using anaesthetized cats. It was found that noradrenaline caused a depression of the magnitude of the pressor response and this effect was antagonized by subsequent injection of piperoxane i.c.m. In contrast, clonidine had no significant effect on the magnitude of the somatic pressor reflex but caused a dose-dependent prolongation of the reflex after cessation of nerve stimulation. This prolongation was antagonized by piperoxane which also caused an increase in the magnitude of the reflex. Piperoxane alone had no significant effect on the magnitude or duration of the reflex. Neither magnitude nor duration of the somatic pressor reflex was influenced significantly by a reduction in resting blood pressure. It is suggested that clonidine and noradrenaline act at different sites within the central nervous system to produce qualitatively different changes in the efferent sympathetic discharge pattern modulating the somatic pressor reflex.

Adrenergic alpha-Agonists↗
PubMed1977

The effects of labetalol (AH 5158) on adrenergic transmission in the cat spleen.

1. The competitive alpha- and beta-adrenoceptor blocking agent labetalol, in concentrations up to 10(-4) M, produced dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 and 30 Hz. 2. At concentrations above 10(-4) M labetol produced a pronounced decrease in transmitter overflow. 3. Labetalol (1.5 X 10(-4) M) increased the recovery of 3H label in the venous blood following the close-arterial infusion of [3H]-(-)-noradrenaline indicating that the drug inhibits uptake of the amine. 4. Both labetalol (3.8 X 10(-5) M) and piperoxan (7.4 X 10(-6) M) produced parallel shifts to the right of the dose-response curves to noradrenaline and oxymetazoline in isolated strips of cat splenic capsule. In this preparation both drugs acted as competitive postsynaptic alpha-adrenoceptor blocking agents. 5. Labetalol (3.3 X 10(-5) M) increased the transmitter overflow following stimulation of the splenic nerves with 200 impulses at 10 Hz. The overflow could be further increased by subsequent addition of piperoxan (7.2 X 10(-6 M). Piperoxan (5.7 X 10(-6) M) alone produced a marked increase in transmitter overflow which could be further increased by subsequent addition of desmethylimipramine (DMI; 3.2 X 10(-5) M). Cocaine (1.5 X 10(-5) M) or DMI (5.4 X 10(-5 M) produced a small increase in transmitter overflow which was not further increased by addition of labetalol (2.8 X 10(-5) M). 6. Labetalol produced a biphasic effect on the responses of the isolated blood perfused spleen of the cat to nerve stimulation. With low doses (up to 10(-4) M) vascular responses were potentiated and with high doses (greater than 10(-4) M) inhibited. The potentiation was related to uptake blockade and the inhibition to decreased transmitter overflow and postsynaptic alpha-adrenoceptor blockade. 7. Labetalol appears to act as a postsynaptic alpha-adrenoceptor antagonist in the isolated blood perfused spleen of the cat with little effect on presynaptic alpha-adrenoceptors. The moderate elevation of transmitter overflow by the drug is related to the inhibitory effect of the drug on neuronal uptake rather than on presynaptic alpha-adrenoceptors.

Animals↗
PubMed1976

Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents.

The influence of clonidine on alpha-adrenoreceptors in the central nervous system of rats and mice has been investigated. Both functional events due to postsynaptic receptor stimulation (flexor reflex activity, motor activity) and biochemical changes have been considered. 1. Clonidine was less potent in stimulating the hindlimb flexor reflex activity of spinal rats than in inhibiting the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and in the whole brain of rats. 2. The increase in flexor reflex activity due to clonidine (0.4 mg/kg) was virtually completely inhibited by phenoxybenzamine (20 mg/kg) and haloperidol (10 mg/kg), was partially inhibited by yohimbine (10 mg/kg) and piperoxan (60 mg/kg) and was not significantly inhibited by yohimbine (3 mg/kg) and tolazoline (50 mg/kg). 3. The potentiation by clonidine of the apomorphine-induced locomotor stimulation of reserpine-treated mice was almost completely inhibited by phenoxybenzamine (20 mg/kg) but was not significantly affected by yohimbine (10 or 3 mg/kg) and only slightly inhibited by tolazoline (50 mg/kg). 4. Clonidine (0.1 mg/kg) caused a considerable inhibition of the alpha-methyltyrosine-induced disappearance of noradrenaline in the spinal cord and brain or rats and in the brain of mice. This effect of clonidine was completely antagonized by yohimbine (10 mg/kg). It was markedly antagonized by yohimbine (3 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg) or haloperidol (10 mg/kg). 5. Clonidine (0.1 mg/kg) caused an inhibition of the accumulation of Dopa after decarboxylase inhibition in the noradrenaline-rich regions of the rat central nervous system. This effect was counteracted by yohimbine (10 mg/kg), piperoxan (60 mg/kg) or tolazoline (50 mg/kg) but not by phenoxybenzamine (20 mg/kg). 6. The postsynaptic functional effects and the biochemical effects of clonidine may be due to stimulation of different alpha-adrenoreceptors since the two effects were inhibited differently by various alpha-adrenoreceptor blocking agents and since the two effects were produced by different doses of clonidine. The alpha-adrenoreceptors mediating the biochemical changes might be located on the noradrenergic neurones.

Adrenergic alpha-Antagonists↗
PubMed1978

Pharmacological characterization of the presynaptic alpha-adrenoceptors regulating cholinergic activity in the guinea-pig ileum.

1 The presynaptic alpha-adrenoceptors located on the terminals of the cholinergic nerves of the guineapig myenteric plexus have been characterized according to their sensitivities to alpha-adrenoceptor agonists and antagonists.2 Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea-pig ileum caused a twitch response. Clonidine caused a concentration-dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine.3 The twitch-inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 mug/ml).4 Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD.5 Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA(2) values of 8.51, 7.78, 7.64 and 6.57 respectively.6 Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch-inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic alpha-adrenoceptors.7 Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch.8 The results demonstrate that the presynaptic alpha-adrenoceptors in the guinea-pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are alpha(2)-adrenoceptors and are different from those located postsynaptically.

Acetylcholine↗
PubMed1979

Suppression of vasopressin secretion by clonidine: effect of alpha-adrenoceptor antagonists.

Studies were performed in anesthetized dogs to determine if the diuretic effect of clonidine results from inhibition of vasopressin secretion. Intravenous clonidine (30 microgram/kg) decreased plasma vasopressin concentration (as measured by RIA) from 10.9 +/- 1.5 to 5.0 +/- 1.1 ng/ml (P less than 0.01) in association with a transient increase in arterial blood pressure and a decrease in heart rate. Intravenous administration of two alpha-adrenoceptor antagonists, piperoxane and phentolamine, virtually abolished the pressor effect of clonidine but did not prevent the suppression of plasma vasopressin concentration. Clonidine decreased plasma vasopressin concentration from 11.9 +/- 3.1 to 3.3 +/- 1.0 pg/ml in the phentolamine-treated dogs (P less than 0.01) and from 18.1 +/- 4.5 to 12.4 +/- 3.6 pg/ml in the piperoxane-treated dogs (P less than 0.05). These results provide direct evidence that the diuretic effect of clonidine results from inhibition of the secretion of vasopressin. This inhibition does not appear to be a consequence of the pressor effect of the drug but may result from a direct action in the central nervous system.

Animals↗
PubMed1990

Spinal alpha 1- and alpha 2-adrenoceptors mediate facilitation and inhibition of spinal motor transmission, respectively.

The role of descending noradrenergic fibers in the spinal motor systems was investigated using spinal reflexes in acutely spinalized rats. In rats pretreated with the MAO inhibitor clorgyline-HCl (1 mg/kg, i.v.), L-3,4-dihydroxyphenylalanine (L-dopa) (5 mg/kg, i.v.), a precursor of dopamine and noradrenaline, markedly potentiated the mono- (MSR) and polysynaptic reflexes (PSR). Selective blockade of alpha 1-adrenoceptors by pretreatment with prazosin-HCl abolished these facilitatory effects on the MSR and the PSR and revealed the inhibitory effect of L-dopa on the PSR. The depression of PSR was antagonized by the alpha 2-antagonist piperoxan. Clonidine-HCl (0.05 mg/kg, i.v.), a so-called alpha 2-agonist, and tizanidine-HCl (0.1 mg/kg, i.v.) decreased the MSR and the PSR in rats pretreated with prazosin. These inhibitions were antagonized by piperoxan. These results suggest that alpha 1- and alpha 2-adrenoceptors mediate facilitation and attenuation of motor transmission in the rat spinal cord, respectively.

Animals↗
PubMed1976

Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents.

The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline.

Adrenergic alpha-Antagonists↗
PubMed1976

Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system.

The activity of serotonergic (5HT) neurons in the dorsal raphe nucleus was inhibited by the i.v. administration of certain antipsychotic drugs (methiothepin, clozapine and thioridazine). However, other antipsychotic agents (chlorpromazine, haloperidol and pimozide) did not inhibit raphe cell firing. The inhibitory potency of these drugs on raphe activity correlates with reported central noradrenergic blocking efficacy. An alpha-adrenergic blocking agent, piperoxane, but not the beta-blocking agents, propranolol and MJ 1999, inhibited raphe activity when administered systemically. All of these drugs appear to act indirectly since they (and NE) have relatively weak or variable effects when applied microiontophoretically to raphe neurons. The depressant effects of certain antipsychotic drugs and piperoxane on 5HT neurons appears to be mediated by a cnetral adrenergic system since (1) the depression could be reversed by the catecholamine releasing agents 1- and d-amphetamine; (2) the depression could be abolished by destruction of adrenergic pathways in the CNS by chemical, mechanical, or electrothermic lesions. While a precise localization has not yet been obtained, the data suggest that these drug effects may be mediated by an adrenergic pathway ascending from the lower brainstem.

Animals↗
PubMed1978

Antagonism by mianserin and classical alpha-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine.

Antagonism of pressor responses to sympathetic outflow stimulation and alpha-adrenoceptor agonists in pithed spontaneously hypertensive rats was used to estimate postsynaptic alpha-adrenoceptor blocking activity of mianserin, phentolamine, phenoxybenzamine, piperoxan and yohimbine. Estimation of presynaptic alpha-adrenoceptor blocking activity of these drugs was obtained by studying their ability to antagonize clonidine-induced suppression of positive chronotropic responses to sympathetic outflow stimulation. In this manner, evidence was obtained that mianserin causes selective presynaptic alpha-adrenoceptor blockade. Mianserin, piperoxan and yohimbine antagonized clonidine-induced avoidance blockade or hypotension in spontaneously hypertensive rats, but methysergide, phenoxybenzamine and phentolamine were ineffective. These results suggest that mianserin may antagonize the central effects of clonidine by blockade of noradrenergic presynaptic or autoreceptors and possibly explain the antidepressant effect of mianserin as due to indirect activation of central noradrenergic neurons.

Adrenergic alpha-Antagonists↗
PubMed1978

Cardiovascular responses to intraventricular adrenaline in spontaneous hypertensive rats.

The effects of intracerebroventricular (i.c.v.) injections of adrenaline on the blood pressure and heart rate of spontaneous hypertensive (SH) rats have been investigated. Adrenaline induced dose-related falls in blood pressure and heart rate in both conscious and urethane anaesthetised rats. In conscious rats, the hypotension and metoprolol, but were unaffected by pretreatment with phentolamine, piperoxan, fluphenazine or methysergide. However, in urethane-anaesthetised rats, the hypotension and bradycardia induced by i.c.v. adrenaline was not significantly affected by i.c.v. pretreatment with propranolol or oxprenolol, while metoprolol significantly antagonised only the bradycardia. Piperoxan, fluphenazine and methysergide were also without effect. Pretreatment with mecamylamine (i.p.) abolished the cardiovascular depressor effects of i.c.v. adrenaline in both conscious and urethane anaesthetised SH rats. It is concluded that the cardiovascular depressor effects of i.c.v. adrenaline are mediated by central adrenoceptors in SH rats and that, in conscious rats, these depressor effects may be mediated by central beta-adrenoceptors rather than alpha-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1992

The effect of adrenergic drugs on serotonin metabolism in the nucleus raphe dorsalis of the rat, studied by in vivo voltammetry.

The serotonin (5-HT) and norepinephrine (NE) system participate in the control of behavioural functions. The experiments were aimed at the question whether the NE system of the locus coeruleus interferes with the 5-HT activity of the nucleus raphe dorsalis and of which receptors are possibly involved. The alpha 1- and beta-adrenoceptor agonists methoxamine and isoproterenol, as well as a high dose (600 micrograms/kg i.p.) of the alpha 2-adrenoceptor agonist clonidine, increased extraneuronal 5-hydroxyindoleacetic acid (5-HIAA) levels in the nucleus raphe dorsalis as measured by in vivo voltammetry. In contrast, a low dose (60 micrograms/kg i.p.) of clonidine and the alpha 1-, alpha 2- and beta-adrenoceptor antagonists, prazosin, piperoxane, and atenolol, reduced the 5-HIAA concentration. In the locus coeruleus, the origin of NE projections to the nucleus raphe dorsalis, clonidine decreased whereas piperoxane enhanced extracellular 3,4-dihydroxyphenylacetic acid (DOPAC), an index of NE metabolism in the locus coeruleus. The results suggest that 5-HT neurotransmission in the nucleus raphe dorsalis is stimulated by the NE system of the locus coeruleus and that adrenoceptor drugs may affect 5-HT neuronal activity in addition to NE neurotransmission.

3,4-Dihydroxyphenylacetic Acid↗