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PubMed1992

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation.

Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease.

Adolescent↗
PubMed1992

Calcium channel blocker-like action of reserpine in smooth muscle.

The effect of reserpine on vascular and intestinal smooth muscles was examined. In these muscles, reserpine inhibited the high K(+)-induced contraction, and this inhibitory effect was antagonized by the increase in external Ca2+ concentration and also by a Ca2+ channel activator, Bay k8644. In rabbit aorta, increases in cytosolic Ca2+ level and muscle tension due to high K+ were inhibited in parallel by reserpine. These results suggest that reserpine inhibits L-type Ca2+ channels to inhibit smooth muscle contraction.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Reserpine inhibits the NaK ATPase activity of the stria vascularis in the cochlea.

The function of the stria vascularis in the cochlea is believed to be the production of endolymph. The mechanisms that maintain or control the function of the stria vascularis, however, remain unclear. In the present study, the effects of one-shot reserpine administration on the NaK ATPase activity of the stria vascularis in guinea pigs were investigated. NaK ATPase activity was shown to be completely inhibited 3 to 20 days after reserpinization, and was detectable again 60 days after reserpinization. As reserpine is an adrenergic neuron blocker, these results suggest that catecholamines may play an essential role in the maintenance or control of NaK ATPase activity, and that the stria vascularis may be one of the target organs of catecholamines.

4-Nitrophenylphosphatase↗
PubMedDate not supplied

Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced catatonia in mice.

Reserpine-induced catatonia is a widely accepted animal model of Parkinson's disease. In the present study, reserpine (5 mg/kg i.p.) and alpha-methylpara-tyrosine (AMPT) (200 mg/kg i.p.) induced catatonia in mice 20 h and 1 h before the experiment, respectively, as assessed using the rota-rod and bar tests after reserpine treatment. There was a significant decrease in fall-off time in the rota-rod test and a significant increase in time spent on the bar in the bar test as compared to the untreated control mice. Combination therapy with L-DOPA (100 mg/kg i.p.) and carbidopa (10 mg/kg i.p.) was less effective in reversing catatonia as compared to higher doses of L-DOPA (200 mg/kg i.p.) and carbidopa (20 mg/kg i.p.), which showed intense hyperactivity in reserpinized mice. Pretreatment with nitecapone (30 mg/kg i.p.), a COMT inhibitor, or selegiline (10 mg/kg i.p.), a MAO-B inhibitor potentiated the motor stimulant actions of subthreshold doses of the L-DOPA (100 mg/kg i.p.) and carbidopa (10 mg/kg i.p.) combination. Amantadine (40 mg/kg i.p.), but not bromocriptine, potentiated the effects of L-DOPA treatment. The NMDA antagonistic action of amantadine may have beneficial effects. It is concluded that COMT and MAO-B enzymes play an important role in the metabolism of dopamine and administration of a COMT or MAO-B inhibitor may prove to be a better adjunct to L-DOPA therapy than a dopamine receptor agonist in Parkinson's disease.

Animals↗
PubMed1979

Effects of ergocornine and reserpine on metamorphosis in Bufo bufo japonicus tadpoles.

Effects of ergocornine and reserpine on tail resorption during metamorphosis in Bufo bufo japonicus tadpoles were studied. At prometamorphosis, ergocornine induced precocious tail resorption, while reserpine scarcely affected the tail size. At the climax of metamorphosis, ergocornine was almost ineffective in accelerating tail resorption, while reserpine was effective in inhibiting tail resorption. Since prolactin-like hormone is known to block the tail resorption induced by thyroid hormones, it was postulated that the release of the hormone is blocked by ergocornine during prometamorphosis and stimulated by reserpine during climax.

Animals↗
PubMed1994

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy.

Subtotal adrenalectomy was given to 10 adult patients with Cushing's disease, concurrently with or following therapeutic regimen by long term reserpine administration and pituitary irradiation. In the present study, we describe long term follow-up results. Two patients died after the operation due to acute adrenal crisis and pneumonia, respectively. The other 8 patients achieved clinical and biochemical remissions and were followed for long term. Three patients relapsed 9, 14 or 17 years after achieving remission, two patients developed hypopituitarism 12 or 20 years after and one died of cerebral vascular accident at 64 years, 5 years after the remission. The remaining 2 patients maintained remission for 10 or 18 years, respectively. During the remission periods of 0.5 to 20 years with a mean of 10.1 +/- 6.7 years, 6 of 7 patients examined by 1 mg overnight dexamethasone test showed normal suppressibility of plasma cortisol. Provocative tests of plasma GH by l-arginine infusion and/or insulin-induced hypoglycemia were performed in 6 patients in the early remission period. All of 5 patients in the arginine infusion test and 3 of 5 in the insulin-induced hypoglycemia test showed normal responses. Furthermore, to facilitate prediction of long term response or failure to our therapeutic regimen, long term reserpine administration and pituitary irradiation, pretreatment clinical and biochemical characteristics were analyzed retrospectively in 3 divided groups; the present 10 patients treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy, 11 patients achieving long term remission treated by our regimen alone, and 7 patients failed with our regimen alone. There were no significant factors predictive of response to our regimen. These findings suggest that subtotal adrenalectomy does not lead favorable outcome, however, reserpine administration shows usefulness to improve pituitary functions in treating Cushing's disease.

Adolescent↗
PubMedDate not supplied

Central nervous system toxicity of manganese. II: Cocaine or reserpine inhibit manganese concentration in the rat brain.

Manganese concentrates in the ventral mesencephalon of male Sprague-Dawley rats after intrathecal administration of MnCl2. We tested the hypothesis that Mn concentration in the central nervous system (CNS), particularly in the ventral mesencephalon, is decreased by inhibiting dopamine reuptake using cocaine or by decreasing dopamine concentrations using reserpine. The intrathecal administration of Mn (250 micrograms Mn/rat as MnCl2) caused the Mn concentration in the ventral mesencephalon to increase from 0.57 to 31.8 micrograms Mn/g. Cocaine administration (8.6 mg/kg i.p.) thirty minutes prior to MnCl2 decreased ventral mesencephalon Mn to 3.3 micrograms Mn/g. By giving reserpine (5 mg/kg i.p.) 24 hours prior to MnCl2 the ventral mesencephalon Mn concentration was decreased from 29.9 micrograms Mn/g to 3.7 micrograms Mn/g. Intrathecal MnCl2 decreased the dopamine concentration in the caudate putamen by 40% six hours after administration. Cocaine or reserpine decreased the Mn concentration in the ventral mesencephalon, occipital pole, frontal lobe and caudate putamen but did not change the Mn concentration in the cerebellum. The results indicate that the mechanism(s) by which Mn is concentrated in many brain regions can be inhibited by cocaine, a dopamine reuptake inhibitor, or by reserpine, a dopamine depleter, and suggest that the Mn concentration in the CNS is related to dopamine reuptake and/or concentration.

Adrenergic Uptake Inhibitors↗
PubMed1975

Pharmacological actions of some simple analogues of reserpine. II. Anticonvulsant effects.

Reserpine analogues obtained from strip-down parts of the parent molecule were studied for their effects on experimental convulsive seizures and amphetamine antagonism. The unsubstituted and M-methoxy substituted piperidino- and morpholino acetanilides derived from A, B and C rings or reserpine showed prominent anticonvulsant activity as against the known lowering of threshold activity by reserpine. Methoxy morpholino derivative showed prominent activity with least sedative effect. gamma-Piperidino acetanilide showed a dual effect such that at higher doses it itself produced clocin covulsions. The effects were non-specific since they unpreferentially antagonized the maximal electrochock, Metrazol and strychnine convulsions Compounds derived from C, D and E rings of reserpine did not significantly increase or decrease the seizure thresholds.

Amphetamine↗
PubMed1975

The involvement of corticosteroids in the supersensitivity produced in the rat anococcygeus muscle by morphine withdrawal, thyroidectomy or a single dose of reserpine.

The effects of chronically administered corticosterone on the responses of the rat isolated anococcygeus muscle to agonists (acetylcholine, norepinephrine) were compared with those of morphine withdrawal in intact or metyrapone-pretreated rats and with those of a single dose of reserpine in intact or adrenalectomized rats. The possibility that the similar supersensitivity, which occurs in thyroidectomized rats, might be associated with elevated corticosterone levels was investigated by measuring fluorimetrically the plasma levels of corticosterone in thyroidectomized rats. Corticosterone, morphine withdrawal or a single dose of reserpine produced similar supersensitivities, characterized by increased maximum responses to both agonists (acetylcholine, norepinephrine) and an increased pD2 value for acetylcholine. This effect of morphine withdrawal together with the weight loss characteristic of this condition was absent in metyrapone-pretreated rats. A single dose of reserpine had no effect in adrenalectomized rats. Plasma corticosterone levels were elevated in thyroidectomized rats. These results suggest that the common factor underlying the identical supersensitivities produced by corticosterone, morphine withdrawal, a single dose of reserpine or thyroidectomy is the ability of each treatment to raise plasma corticosterone levels.

Acetylcholine↗
PubMed1975

The effect of antidepressants on the calcium content of the aorta of reserpine-treated rabbits.

The pre-administration of reserpine in a dose of 5 mg/kg b.o. i.v. 24 before the experiment reduced the calcium content of the thoracic aorta of rabbits weighing 1,000--1,500 g. It had no effect on the calcium level in older animals. The calcium content also fell after 10 days' administration of reserpine in daily doses of 0.1 mg/kg b.w. Pre-administration of the monoaminooxidase inhibitors phenelsine and nialamide inhibited the reserpine-induced decrease in the calcium content of the vascular wall, although by themselves they had no effect on it. Prothiadene, a thymoanaleptic, likewise inhibited, the decrease in the calcium content when administered per os in a dose of 5 mg/kg b.w. 5 hours before reserpine.

Animals↗
PubMedDate not supplied

Reserpine ulcers in morphine dependent and withdrawal rats.

Reserpine ulcers were produced in dependent and withdrawal rats. The reactivity of isolated duodenum and colon to morphine and papaverine was tested in both groups of animals. Chronic administration of morphine decreases the development of post reserpine gastric ulcers, while in withdrawal rats it increases their occurrence. Relaxation and contraction responses of duodenum taken from the dependent rats showed tolerance. On the other hand, withdrawal rats displayed increased responses as compared with placebo group. Colon of dependent rats showed stronger responses to morphine and papaverine which indicates the lack of tolerance to morphine or enhanced receptors sensitivity. Stronger responses of colon in both dependent and withdrawal rats suggest the lack of tolerance in this segment of the gut. In withdrawal rats which obtained reserpine and placebo responses to papaverine were similar. It is suggested that reserpine decreased the sensitivity of mu receptor to morphine.

Animals↗
PubMed2003

FK506 as effective adjunct to L-dopa in reserpine-induced catalepsy in rats.

Reserpine-induced catalepsy is a widely accepted animal model of Parkinson's disease. In the present study reserpine (2.5 mg/kg, ip) 20 hr and alpha-mehyl-para-tyrosine (AMPT; 200 mg/kg, ip), one hour before the experiment induced significant catalepsy in rats as assessed by bar test. There was a significant increase in the time spent on the bar in bar test as compared to the control untreated rats. L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination, a conventional therapy was less effective in reversing reserpine-induced catalepsy. Pretreatment with FK506, a neuroprotectant (0.5-2 mg/kg, po) not only dose dependently reduced the catalepsy in reserpine-treated rats but a lower dose (1 mg/kg) potentiated the motor stimulant actions of sub threshold dose of L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination. Anticataleptic effect of FK506 was blocked dose dependently by specific D2 receptor blocker sulpiride (25-100 mg/kg, ip). In conclusion, the findings of the present study suggest that FK506 has an indirect modulatory action on the dopamine D2 receptors. FK506 being a neuroprotectant, could be used as an effective adjunct to L-dopa for the treatment of neuroleptic-induced extrapyramidal side effects.

Animals↗
PubMed1991

Neurogenic signals regulate chromaffin cell proliferation and mediate the mitogenic effect of reserpine in the adult rat adrenal medulla.

The adrenal medulla is innervated by nerve fibers from several sources, which synapse on chromaffin cells and stimulate the secretion of catecholamines. The antihypertensive agent reserpine is known to reflexively increase this neurogenic stimulation by depleting catecholamine stores, and long-term administration of reserpine is associated with adrenal medullary hyperplasia and neoplasia. To determine the role of neurogenic signals in regulating normal and reserpine-stimulated proliferation of chromaffin cells, the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into replicating nuclei was assessed in the adrenal medulla of adult rats. Unilateral adrenal denervation caused a 4-5 fold decrease in chromaffin cell labeling by 5-bromo-2'-deoxyuridine during a 2-week labeling period. Denervation also prevented stimulation of labeling in animals receiving reserpine in their diet. These findings suggest that neurogenic control of cell proliferation may play an important role in the pathogenesis of adrenal medullary hyperplasia and neoplasia, and in the normal development of the peripheral and central nervous systems.

Adrenal Medulla↗
PubMedDate not supplied

[Effect of large doses of reserpine on the hypothalamo-hypophyseal-adrenal system in Itsenko-Cushing's disease].

The results of study of the hypothalamo-hypophysio-adrenal system in patients with Itsenko-Cushing's disease under the influence of high reserpine doses are presented. An increase of plasma ACTH and cortizol level and disturbance of the 24-hour rhythm of their secretion was noted in the patients. High reserpine doses led to the fall of ACTH and cortizol secretion, without any normalization of their secretion rhythm in the course of 24 hours. A test with metopyron carried out before and after the reserpine prescription pointed to the increase of the ACTH reserve under the influence of high reserpine doses.

17-Hydroxycorticosteroids↗
PubMed1991

Mucosal changes in mouse duodenum after gamma-irradiation or reserpine treatment.

Although the bulk of the literature implies that most of the radiation-induced effects on small intestine are related to epithelial damage, previous work has indicated that there are structural changes in the neuromuscular component of the wall. The short timescale of changes in villous shape produced by hyperthermia but similar to those seen after radiation, also supports the claim that there is a neuromuscular contribution involved. A preliminary report showed that the radiation-induced changes in the small intestine could be simulated by the administration of reserpine, a drug chosen for its effects on the neuromuscular component of the mucosal wall. A system of villous scoring indicated that the overall effects of the two regimes were approximately equivalent in terms of the changes produced in the shape of the villi. The current paper describes the results of experiments to compare the two regimes over the time scale 1 h to 3 days. The time points were chosen to include likely maximum damage caused by reserpine (18 h after treatment) and radiation (3 days after treatment). Mice were irradiated with 15 Gy gamma-rays from a 60Co source or treated with reserpine (1 mg/kg and 16 mg/kg). Scanning electron microscopy showed some changes in the duodenal mucosal topography of some control groups which may be related to the stress of treatment and are in keeping with previous findings. However, the changes seen in treated groups were greater than those found in the corresponding control samples. The overall villous changes were plotted using a grid score method, which showed that both radiation and reserpine treatment altered the villous morphology in a similar way. Light microscopy and transmission electron microscopy showed that smooth muscle damage was associated with the villous collapse. The work indicates that the intestinal wall can be damaged by many agents and that greater understanding of radiation-induced damage can be gained by comparing it with that produced in other ways.

Animals↗
PubMed1975

Antihypertensive drugs and catecholamine metabolism: effects of reserpine and hydralazine on tyrosine hydroxylase activity and norepinephrine concentrations in the spontaneously hypertensive rat.

The antihypertensive drugs, reserpine and hydralazine, produce different effects on tyrosine hydroxylase activity and norepinephrine levels in blood vessels and other tissues of the spontaneously hypertensive rat at doses which cause an equivalent reduction in blood pressure. Reserpine administration is associated with increased tyrosine hydroxylase activity in the mesenteric artery, mesenteric vein and adrenal, but the vasculature appears more sensitive to the effects of reserpine than the adrenal. This increase in tyrosine hydroxylase activity can be related to catecholamine depletion in the mesenteric artery, mesenteric vein and adrenal. Since chlorisondamine, a ganglionic blocking agent, diminished the ability of reserpine to increase tyrosine hydroxylase activity in the mesenteric artery and adrenal, it is likely that increased nerve activity is involved in regulation of the enzyme in both tissues. Hydralazine neither alters tyrosine hydroxylase activity in arteries or veins, nor depletes catecholamine levels in these tissues. In the adrenal, hydralazine increases tyrosine hydroxylase activity independently of any change in catecholamine levels. It would appear that changes in tyrosine hydroxylase activity produced by antihypertensive drugs are organ dependent and may involve both neuronal activity and amine depletion.

Adrenal Glands↗
PubMed1975

Time course of the effect of reserpine administration on tyrosine hydroxylase activity in adrenal glands and vasa deferentia.

During the first several hours after administration of reserpine, tyrosine hydroxylase activity in rat adrenal slices and in isolated intact vasa deferentia of mice and rats is profoundly reduced, although no effect on enzyme activity in isolated fortified homogenates of these tissues is demonstrable. This effect, observed only in intact preparations, is competitively antagonized by addition to the medium of the synthetic pterin cofactor, 6,7-dimethyltetrahydropterin (DMPH4). Kinetic analysis of the effect of acute reserpine treatment on tyrosine hydroxylase activity in these isolated, intact tissues indicates that the Km for the pterin cofactor is increased but the Vmax is not altered. The results indicate that reserpine produces its inhibition of tyrosine hydroxylase by preventing catecholamine storage and causing elevated levels of free intraneuronal norepinephrine. The catecholamine inhibits the enzyme in a manner which is competitive with the pterin cofactor. After more chronic reserpine treatment, when catecholamine stores are severly depleted, this inhibition of tyrosine hydroxylase activity in intact tissues is no longer apparent. After 3 days of treatment, increased levels of tyrosine hydroxylase are demonstrable in the adrenal glands of rats but not in the vass deferentia of either mice or rats. The increased enzyme levels in the adrenal gland are presumably due to increased enzyme formation.

Adrenal Glands↗
PubMed1989

Effect of the post-reserpine adrenergic block on thrombocytopoiesis and thrombocyte aggregation in rats.

The effect of the post-reserpine adrenergic block (2 mg/kg for 3 and 6 days) on thrombocytopoiesis, bone marrow megakaryocytes (MKC) and thrombocyte aggregation was studied. A slight decrease in thrombocytes and a significant inhibition of 75selenomethionine incorporation in the newly-formed thrombocyte, more pronounced after 6-day reserpine treatment, was observed. The megakaryocytogram of the rats treated with reserpine for 3 and for 6 days manifested a similar significant decrease in MKC--as a total number and their separate stages. Thrombocyte aggregation was significantly inhibited, especially after the 6-day treatment. The inhibition of the megakaryocytopoiesis is probably the result of reduced metabolic processes, while thrombocyte aggregation probably results also from the serotonin depletion in the thrombocytes and the increased adrenaline level in the blood--phenomena observed after treatment with reserpine. It is concluded that the normal functions of the neuronal unit of the adrenergic transmitter system are necessary for the formation of an adequate number of functionally valuable thrombocytes.

Animals↗