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L X Cubeddu

Publications and source records attributed to L X Cubeddu.

At least 91 records · Page 5Linked to original sources
PubMed1986

Dopamine autoreceptors modulate dopamine release from the prefrontal cortex.

Electrical stimulation (at 0.3, 1, or 10 Hz, 120 pulses each) produced a calcium-dependent overflow of radioactivity from slices of the rabbit prefrontal cortex preloaded with [3H]3,4-dihydroxyphenylethylamine ([3H]DA, [3H]dopamine) in the presence of desipramine. Flat frequency-release curves were observed. Apomorphine and LY-171555 inhibited in a concentration-dependent fashion the evoked overflow of DA, an effect antagonized by haloperidol. Stimulation frequencies comparable to normal firing rates of mesocortical neurons (10 Hz) drastically reduced apomorphine-induced inhibition of DA overflow. Haloperidol produced greater facilitation of DA overflow at 10 than at 1 Hz. Nomifensine, a neuronal uptake inhibitor, enhanced DA overflow. These results indicate that mesocortical DA neurons projecting to the prefrontal cortex have release modulatory autoreceptors of the D2 subtype.

Animals↗
PubMed1986

Interactions between endogenous dopamine and dopamine agonists at release modulatory receptors: multiple effects of neuronal uptake inhibitors on transmitter release.

The authors investigated the mechanisms by which inhibitors of the neuronal uptake (NUI) of dopamine (DA) and prolonged stimulations at high rates antagonize the inhibition of acetylcholine (ACh) release from rabbit striatal slices produced by DA receptor agonists. Nomifensine (1 microM) reduced the potency and efficacy of apomorphine (APO) in inhibiting the evoked release of ACh (0.3 Hz, 39 pulses) (noncompetitive kinetics). Highest inhibitory potency and efficacy of APO were obtained at 0.3 Hz and 39 pulses. Increases in stimulation rates and number of pulses (3 Hz and 120 pulses) reduced APO potency and efficacy for inhibition of ACh release (noncompetitive kinetics). At 10 Hz and 500 pulses APO efficacy was further reduced, and the APO concentration-effect curve was biphasic. Inhibition of DA and ACh release produced by other DA receptors agonists such as bromocriptine, piribedil and LY-171555 was also reduced by prolonged stimulations at high frequencies. Depletion of endogenous DA stores by reserpine pretreatment abolished the antagonism of APO produced by NUI and reduced considerably the antagonism produced by high pulses and high rates of stimulation of APO- and LY-171555-induced inhibition of ACh release. However, even after combined pretreatment with reserpine and alpha-methylparatyrosine, the potency and efficacy of APO in inhibiting ACh release at 10 Hz and 500 pulses were less than the values obtained in 0.3 Hz and 39 pulses and at 3 Hz and 120 pulses. The biphasic nature of the APO concentration-effect curve at 10 Hz and 500 pulses was no longer present after reserpine. Interestingly, reserpine pretreatment failed to modify APO-induced inhibition of ACh release at 0.3 Hz and 39 pulses, suggesting that the sensitivity of the DA release modulatory receptors was not affected by the pretreatment. These results indicate that the high synaptic concentration of DA achieved at low stimulation rates in the presence of NUI and at high stimulation rates reduces the potency and efficacy of DA agonists in inhibiting ACh release. However, for prolonged stimulations at high rates not all of the changes seen with DA agonists are mediated by endogenous DA. At high concentrations (10 microM), cocaine and nomifensine inhibited the evoked release of ACh even after depletion of tissue DA stores by reserpine in the absence or presence of a alpha-methylparatyrosine.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1986

Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. I. Release in the absence of vesicular transmitter stores.

The release of endogenous dopamine (DA) elicited by electrical stimulation and by d-amphetamine (AMPH) from superfused striatal slices of reserpine-pretreated rabbits was examined. Although reserpine pretreatment reduced tissue DA levels by greater than 95%, the basal efflux of DA and the DA metabolite dihydroxyphenylacetic acid (DOPAC) was slightly greater than that observed in untreated slices. DOPAC constituted the large majority of the basal efflux of endogenous compounds. No overflow of endogenous compounds was evoked by electrical stimulation (3 Hz, 3 min) after reserpine pretreatment. Superfusion with alpha-methyl-p-tyrosine (100 microM) abolished the efflux of endogenous DA and DOPAC. AMPH (0.3-10 microM) produced a concentration-dependent increase in the basal efflux of endogenous DA and a concomitant decrease in endogenous DOPAC efflux. The total efflux of endogenous compounds (DA + DOPAC) tended to be decreased by AMPH. No electrically evoked overflow of endogenous compounds was observed in the presence of AMPH. The increase in synaptic DA produced by AMPH was reflected by a concentration-dependent reduction in the electrically evoked overflow of [3H]acetylcholine (ACh). The ability of AMPH to increase DA efflux and inhibit [3H]ACh release was blocked by inhibition of DA synthesis with alpha-methyl-p-tyrosine (100 microM) or by blockade of the DA neuronal uptake carrier with nomifensine (NOM) (10 microM) and was potentiated by inhibition of monoamine oxidase with pargyline (10 microM). NOM also blocked partially the ability of AMPH to reduce endogenous DOPAC efflux. NOM increased the basal efflux of endogenous DA and inhibited electrically evoked [3H]ACh release but these effects were quantitatively much less than those produced by AMPH. NOM had no effect on DOPAC efflux. Pargyline had little effect on endogenous DA efflux or electrically evoked [3H]ACh release but abolished DOPAC efflux and increased tissue DA levels measured at the end of superfusion. When given in combination, NOM and pargyline produced a similar degree of inhibition of [3H]ACh release as AMPH, although the increase in DA efflux produced by this drug combination was less than that produced by AMPH. These results suggest that in the absence of vesicular transmitter stores (reserpine-pretreatment): synthesis provides a continuous supply of DA which is metabolized rapidly within the neuron and is lost as DOPAC; AMPH facilitates the synthesis-dependent efflux of extravesicular DA probably by an accelerated exchange diffusion mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. II. Release in the presence of vesicular transmitter stores.

The release of endogenous dopamine (DA) elicited by electrical stimulation and by d-amphetamine (AMPH) from superfused striatal slices of untreated rabbits was examined. AMPH (0.3-10 microM) produced a concentration-dependent increase in basal DA efflux (30-fold increase at 10 microM) and stimulation-evoked (SE) DA overflow (11-fold increase at 10 microM). Although AMPH had little effect on the basal efflux of dihydroxyphenylacetic acid (DOPAC), the drug was an effective inhibitor of the SE overflow of the DA metabolite (66% inhibition at 0.3 microM). AMPH increased significantly the total basal efflux of endogenous compounds (DA + DOPAC) only at high concentrations (3-10 microM) whereas the total SE overflow of total endogenous compounds was decreased at all concentrations of AMPH tested. AMPH inhibited SE [3H]acetylcholine (ACh) release in a concentration-dependent manner (71% inhibition at 10 microM). Inhibition of DA synthesis with alpha-methyl-p-tyrosine (100 microM) or 3-iodotyrosine (100 microM) reduced both the basal efflux and SE overflow of endogenous DA and DOPAC; synthesis inhibition had greater effects on the SE overflow. Neither synthesis inhibitor altered SE [3H]ACh release. alpha-Methyl-p-tyrosine and 3-iodotyrosine reduced the absolute values of the basal efflux and SE overflow of DA elicited by AMPH by approximately 60%; however, the inhibition of SE [3H]ACh release produced by AMPH was attenuated only slightly (approximately 20%). Synthesis inhibitors also reduced tissue DA levels (approximately 30%). These results suggest that: basal efflux of endogenous DA from superfused rabbit striatal slices may derived both from DA newly synthesized in the cytoplasm and from spontaneous leakage of DA from storage vesicles. In addition, synthesis may provide a continuous supply of DA to vesicles that are used for exocytotic DA release during electrical stimulation. However, the depletion of tissue DA produced by synthesis inhibitors as well as other extraneous pharmacological actions of these drugs makes firm conclusions difficult. AMPH increases the synaptic concentration of DA by accelerating the basal efflux as well as the SE overflow of unchanged DA. At concentrations less than 1 microM AMPH has no effect on basal efflux of DA or DOPAC but reduces SE overflow of DOPAC via an unknown mechanism. At higher concentrations (greater than or equal to 1 microM) acceleration of carrier-mediated DA efflux coupled with displacement of DA from vesicular stores, as well as interference with the uptake of exocytotically released DA produces a marked increase in synaptic DA which in turn inhibits SE ACh release.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Beta blockade by oral propranolol and labetalol.

beta-Adrenergic blockade after single, oral doses of labetalol or propranolol was evaluated in a double-blind, placebo-controlled study by an isoproterenol sensitivity test and handgrip exercise in 10 healthy men. The tests were performed with subjects resting in a supine position. At the doses used, there was no effect on heart rate and blood pressure in either the resting position or in the isometric exercise phase. It is possible that exercise-induced changes in blood pressure and heart rate were reduced by higher vagal tone in this young group tested in the supine position. Isoproterenol increased heart rate and reduced diastolic blood pressure in a dose-dependent manner. The dose of isoproterenol at which heart rate increased 25 bpm above the resting rate (CD25; 1.36 +/- 0.18 microgram) was of the order of that at which diastolic blood pressure fell 25 mm Hg from baseline (HD25; 1.07 +/- 0.07 microgram). There was a significant positive correlation between CD25 and HD25 in the 10 subjects. Propranolol and labetalol induced a dose-dependent, parallel shift to the right in the dose-response curves of isoproterenol effects on heart rate and diastolic blood pressure, indicating that both drugs are nonselective, competitive antagonists of beta-adrenergic receptors. On the average, propranolol was 17 and 19 times more potent than labetalol in antagonizing the chronotropic and hypotensive actions of isoproterenol, respectively.

Administration, Oral↗
PubMed1985

Evidence for autoreceptor modulation of endogenous dopamine release from rabbit caudate nucleus in vitro.

This study was designed to determine if the release of endogenous dopamine (DA), like [3H]DA, is modulated by inhibitory autoreceptors. A high-performance liquid chromatographic assay was developed which was capable of detecting the basal efflux and electrically evoked overflow of endogenous DA and dihydroxyphenylacetic acid (DOPAC), the primary DA metabolite. In the absence of neuronal uptake inhibitors the stimulation-evoked overflow of endogenous DA was entirely in the form of DOPAC, whereas overflow consisted primarily of DA in the presence of uptake inhibition. The evoked overflow of DA and DOPAC was abolished by reduction of the Ca++ concentration of the superfusion medium from 1.3 to 0.13 mM. The DA receptor antagonist sulpiride (1 microM) increased DOPAC overflow by 41%. Nomifensine (10 microM) increased slightly and cocaine (10 microM) decreased slightly the total overflow of endogenous compounds (DA plus DOPAC). Combination of nomifensine and sulpiride or cocaine and sulpiride increased total overflow of endogenous compounds by 217 and 120%, respectively, as compared to the neuronal uptake inhibitors alone. The DA receptor agonists apomorphine (0.3 microM) and bromocriptine (1 microM) inhibited DOPAC overflow by 92 and 83%, respectively. However, apomorphine and bromocriptine failed to inhibit endogenous DA release in the presence of nomifensine. Sulpiride antagonized the inhibitory effects of both apomorphine and bromocriptine. In experiments in which [3H]DA and endogenous DA overflow were measured simultaneously, radiolabeled DA behaved exactly like the endogenous transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Clonidine reduces elevated cerebrospinal fluid catecholamine levels in patients with essential hypertension.

Cerebrospinal fluid (CSF) catecholamines were measured in normotensive patients and in patients with mild to moderate essential hypertension. CSF-norepinephrine (NE) concentrations were 50% lower in the normotensive individuals (127 +/- 28 vs. 240 +/- 23 pg/ml) (P less than 0.01). In hypertensive patients, CSF-NE was inversely related to age (r = -0.68; P less than 0.01) and directly related to plasma NE (r = 0.61; P less than 0.05). Clonidine (450 mcg/day for 2 weeks) significantly reduced CSF-NE (-40%) in hypertensive patients. In addition, it decreased blood pressure, plasma and urinary NE. Urinary VMA was not affected by clonidine. No correlation was observed between clonidine effects on BP and on plasma or CSF catecholamines. This study indicates that patients with essential hypertension have elevated levels of CSF-NE which are reduced after treatment with clonidine. The elevation of CSF-NE suggests that central (spinal?) noradrenergic activity may be increased in patients with mild to moderate essential hypertension, and that can be reduced by treatment with clonidine.

Adult↗
PubMed1984

Verapamil and propranolol in essential hypertension.

Twenty-four subjects with mild to moderate essential hypertension completed this 9-wk parallel, randomized, double-blind study of the antihypertensive effects of verapamil (V) (240 to 480 mg%) and propranolol (P) (120 to 360 mg%). V lowered systolic and diastolic blood pressures in all postural positions, with an average reduction of 20/16 mm Hg. With the exception of standing systolic blood pressure, P also lowered systolic and diastolic blood pressures in all postural positions, with an average reduction of 9/11 mm Hg. Differences between V and P were significant only for sitting systolic blood pressure. Heart rate was decreased by P but was not affected by V. The PR interval was prolonged by V. Plasma levels of V and P were directly related to dose. Plasma levels of V were linearly related to those of its major metabolite, norverapamil (r = 0.81). There was no correlation between clinical response and the dose or plasma level of V or P, but all subjects who received 480 mg% V had an average blood pressure reduction of 20/16 mm Hg and plasma levels of the parent drug above 200 ng/ml. V is an effective antihypertensive for mild to moderate essential hypertension. Constipation, pedal edema, and a maculopapular rash were reported as side effects of V.

Adult↗
PubMed1984

Bupropion does not antagonize cardiovascular actions of clonidine in normal subjects and spontaneously hypertensive rats.

Tricyclic antidepressants (TADs) are known to antagonize the hypotensive and sedative actions of clonidine. We compared the effects of bupropion and imipramine pretreatment on the acute hypotensive and sedative actions of clonidine in eight normotensive male subjects in a randomized, double-blind crossover study. Pretreatment with bupropion, 100 mg by mouth three times a day for 9 days, had no effect on baseline supine blood pressure (BP) and heart rate (HR) and did not modify the hypotensive, bradycardic, and sedative actions of clonidine. Imipramine, 25 mg by mouth three times a day for 9 days, increased supine and standing HR and decreased standing systolic BP. In half the subjects the hypotensive action of clonidine was reduced 40% to 50% by imipramine. The specific binding of 3H-yohimbine to alpha 2-receptors of platelet membranes was not affected by pretreatment with either antidepressant. In spontaneously hypertensive rats, 16 days of bupropion, 25 mg/kg subcutaneously, had no effect on baseline BP and HR and did not antagonize the hypotensive and bradycardic effects of clonidine, 5 mg/kg iv. Pretreatment with desipramine, 5 mg/kg subcutaneously for 16 days, accelerated baseline HR and reduced cardiovascular actions of clonidine. These observations suggest that not all antidepressants antagonize the effects of clonidine. If the negative interaction between TADs and clonidine is a result of sensitivity of alpha 2-receptors, these receptor changes are not the common denominator of antidepressant activity and may only be seen with TADs.

Adult↗
PubMed1984

Differential effects of bromocriptine on dopamine and acetylcholine release modulatory receptors.

Rabbit neostriatal slices were prelabeled with [3H]dopamine (DA) and [14C]choline and then superfused. The electrical stimulation-evoked release of DA and of acetylcholine (ACh) was abolished by 0.33 microM tetrodotoxin and by low calcium concentrations (0.13 mM). Bromocriptine, a selective D2-DA receptor agonist, inhibited in a concentration-dependent manner the evoked overflow of DA and ACh, without affecting the basal efflux of both transmitters. The effects of bromocriptine were antagonized by sulpiride, a specific antagonist of D2-DA receptors. With stimulation at 0.3 Hz and 120 pulses, bromocriptine was eight times more potent in inhibiting the evoked overflow of DA (IC50: 11 nM) than that of ACh (IC50: 83 nM). Stimulations at 3 Hz and 360 pulses markedly reduced the potency of bromocriptine in inhibiting DA and ACh release, and diminished its selectivity for presynaptic receptors. These results indicate that DA receptors that modulate the release of DA and ACh are of the D2 subtype. The greater potency of bromocriptine at pre- than at postsynaptic sites suggests that these receptors may be different in quantity and/or quality [D2-alpha (presynaptic) versus D2-beta (postsynaptic)]. Finally, marked differences in the potency and efficacy of DA agonist actions on DA and ACh release modulatory receptors are obtained, depending on the parameters of stimulation used.

Acetylcholine↗
PubMed1984

Greater potency of mesoridazine and sulforidazine compared with the parent compound, thioridazine, on striatal dopamine autoreceptors.

The electrically evoked overflow of dopamine (DA) from perfused rabbit striatal slices was used to assess the relative functional potencies of thioridazine, a phenothiazine antipsychotic agent, and two of its major metabolites, mesoridazine (thioridazine-2-sulfoxide) and sulforidazine (thioridazine-2-sulfone). Thioridazine (1000 nM) enhanced the electrically evoked overflow of DA by 18.3 +/- 4.6% (n = 4) at 0.3 Hz. Mesoridazine and sulforidazine likewise produced only small increases (5-20%) in evoked overflow of DA from slices stimulated at 0.3 Hz. At this frequency of stimulation, apomorphine (30 nM) inhibited the overflow of DA by 71.4 +/- 8.43% (n = 40). All three drugs antagonized, in a concentration-dependent fashion, the inhibitory effect of apomorphine (30 nM) on electrically evoked DA release at 0.3 Hz. The IC50 for thioridazine for antagonizing the effect of apomorphine was 130 nM, whereas that for mesoridazine was 14.4 nM and for sulforidazine was 6.1 nM. These results indicate that thioridazine and its two clinically active metabolites can block striatal DA autoreceptors involved in modulating DA release. The observation that mesoridazine and sulforidazine were significantly more potent than the parent drug is consistent with the hypothesis that a major part of the pharmacologic responses to thioridazine may be a consequence of its metabolism to active compounds.

Animals↗
PubMed1984

Frequency-dependent muscarinic receptor modulation of acetylcholine and dopamine release from rabbit striatum.

The effects of muscarinic receptor activation on the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) or [3H]ACh were investigated in rabbit striatal slices. Release was measured in the presence of 10 microM hemicholinium and 1 microM sulpiride to block choline uptake and prevent the effects of released DA on DA receptors modulating release. Stimulation (120 pulses, 20 mA, 2 msec) at 0.3, 3 and 10 Hz produced (3H or 14C) ACh release that sharply declined with increasing stimulation frequency. A flat frequency-release curve was obtained for DA. Oxotremorine (OXO), a direct muscarinic agonist (1-100 microM), produced a concentration-dependent inhibition of ACh release, inversely related to stimulation frequency, at a fixed number of pulses (120). When the number of pulses was modified to produce similar amounts of ACh release (20 pulses at 0.1 Hz, 39 pulses at 0.3 Hz, 120 pulses at 3 Hz and 350 pulses at 10 Hz), much greater inhibition of ACh release by OXO (0.3 and 3 microM) was obtained with lower frequencies and lower number of pulses. Physostigmine, an acetylcholinesterase inhibitor, decreased ACh release with an inverse relationship to stimulation frequency. Atropine (1 microM), a selective muscarinic antagonist, enhanced the release of ACh more at 10 Hz than at 0.3 and 3 Hz and completely antagonized the effects of OXO (10 microM) and physostigmine (1 microM) at all three stimulation frequencies. OXO (3 and 10 microM) enhanced DA release at 3 Hz. Physostigmine (1 microM) and atropine (1 microM) had no effect on DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1983

Naloxone does not antagonize the antihypertensive effect of clonidine in essential hypertension.

Reports on spontaneously hypertensive rats suggested that naloxone blocked the antihypertensive effects of clonidine. We compared the effects of an 8-hr intravenous naloxone infusion (6 micrograms/kg/hr) or 5% dextrose in water (D5/W) begun 2 hr before single oral doses of clonidine (0.3 mg) in six men with mild to moderate essential hypertension (EHT). Supine and standing (after 5 min) blood pressure (BP) and heart rate (HR) were measured every 20 min. Initial treatment with naloxone or placebo (D5/W) infusion was randomly allocated, with the alternate treatment given 1 wk later. Naloxone did not modify either supine or standing BP or HR. Clonidine induced a gradual, sustained reduction in both supine and standing systolic and diastolic BP and in supine HR, and there was an increase in standing HR. Naloxone did not modify the onset, maximal effect, or recovery of the hypotensive and HR effects of clonidine in both the supine and standing positions. Our data indicate that hypotensive and bradycardiac effects of clonidine in EHT are not mediated by naloxone-sensitive opioid receptors. They also suggest that opioid receptors play no role in the maintenance of hypertension nor in the BP and HR adjustments induced by postural changes in EHT.

Adult↗
PubMed1983

Frequency-dependent release of acetylcholine and dopamine from rabbit striatum: its modulation by dopaminergic receptors.

The release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) was monitored from single slices of the rabbit striatum. In all cases, the evoked overflow of ACh showed a higher peak and was of shorter duration than that of 3H products. For ACh, the release per pulse showed a marked decline with increasing frequency of stimulation, whereas flat frequency-release curves were obtained for DA. At 0.1 and 1 Hz the evoked overflows of ACh were 15 and 7 times greater, respectively, than those of DA. Haloperidol (0.03 microM) and sulpiride (1 microM) produced large increases in the evoked overflow of DA and ACh at 3 and 10 Hz; little effect was observed at lower frequencies. These results indicate that the frequency-release curves for DA and ACh are different and that at high frequencies the slope of the curves is modified by activation of pre- and postsynaptic DA receptors. Apomorphine inhibited in a concentration-dependent fashion the evoked overflow of DA and ACh; greater inhibition was obtained at lower frequencies of stimulation. At 0.3 Hz the DA agonist was two times more potent in inhibiting DA than ACh overflow (IC50: 12.0 +/- 2.2 versus 22.0 +/- 2.8 nM; p less than 0.01). The greater sensitivity of pre- than postsynaptic sites to apomorphine was also seen at higher frequencies (3 Hz). Benztropine (1 microM) reduced the evoked overflow of ACh at 10 Hz, and enhanced that of 3H products at all rates of stimulation (0.3-10 Hz). These results suggest that the release of DA and ACh is regulated by dopaminergic receptors. They also indicate that the effects of DA agonists and antagonists and of uptake inhibitors on DA and ACh release are highly dependent on the frequency of stimulation used.

Acetylcholine↗
PubMed1983

Changes in the sensitivity to apomorphine of dopamine receptors modulating dopamine and acetylcholine release after chronic treatment with bromocriptine or haloperidol.

The release of dopamine (DA) and of acetylcholine (ACh) was monitored from rabbit striatal slices labeled with [3H]DA and [14C]choline. Chronic treatment with haloperidol (1 mg/kg b. wt. for 28 days, sacrifice 96 hr after last injection) increased the potency of in vitro apomorphine in inhibiting the release of DA and ACh evoked by electrical stimulation when compared to vehicle-treated rabbits. Potentiation of apomorphine effects was greater on DA than on ACh release. The effects of in vitro haloperidol on DA and ACh release and in antagonizing the inhibitory effects of apomorphine were not modified by chronic treatment with haloperidol. Bromocriptine (1.5 mg/kg b.wt. for 7 days, sacrifice 72 hr after last injection) did not affect the evoked release of DA and of ACh, or the sensitivity to apomorphine. However, 15 mg/kg b.wt. of bromocriptine for 7 days and sacrifice 72 hr after last injection, produced a 60 to 70% reduction in the evoked release of DA and ACh, and markedly antagonized the inhibition of DA and ACh release produced by apomorphine. These results indicate that the DA receptors which modulate the release of DA and of ACh play an important physiological role inasmuch as they develop adaptational changes after prolonged receptor activation or inhibition by DA agonists and antagonists, respectively. These adaptational changes affect the potency of DA agonists on release modulatory receptors without modifying that of DA antagonists. The possibility that bromocriptine has a residual agonistic effect on striatal DA receptors 3 days after the last injection cannot be ruled out.

Acetylcholine↗
PubMed1982

Prazosin and propranolol in preoperative management of pheochromocytoma.

Combined use of prazosin and propranolol was effective in preoperative management of three patients with norepinephrine(NE)-secreting pheochromocytoma (PHEO). On admission, all were symptomatic and had moderate to severe hypertension despite treatment with diuretics, propranolol, and sympatholytics. Optimal symptomatic and blood pressure (BP) control was achieved with 6 to 10 mg/day prazosin and 120 to 480 mg/day propranolol every 6 hr in equally divided doses. With this therapy, BP and hematocrit were reduced to levels similar to those found in the postoperative period. The daily urinary excretion of catecholamines and their metabolites was not modified during therapy with prazosin and propranolol. There was a drop in supine systolic (40 to 64 mm Hg) and diastolic (32 to 52 mm Hg) BP in all patients 1 to 2 hr after the first dose of prazosin (1-mg tablet); in two subjects this was accompanied by a larger orthostatic fall (74 and 92 mm Hg systolic; 65 and 78 mm Hg diastolic BP). The high incidence of first-dose effect suggests that a single oral dose of 1 mg of prazosin could aid in the diagnosis of PHEO. The effectiveness of prazosin in controlling the hypertension induced by NE-secreting PHEO suggests that, in man, pressure responses to augmented levels of NE are mediated solely through alpha 1-receptors.

Adolescent↗