Reserpine

About: Reserpine is a research topic. Over the lifetime, 6324 publications have been published within this topic receiving 169644 citations. The topic is also known as: Serpalan® & (3beta,16beta,17alpha,18beta,20alpha)-11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester.

The catecholamine hypothesis of affective disorders: a review of supporting evidence

Abstract: The "catecholamine hypothesis of affective disorders" proposes that some, if not all, depressions are associated with an absolute or relative decrease in catecholamines, particularly norepinephrine, available at central adrenergic receptor sites. Elation, conversely, may be associated with an excess of such amines. Evidence supporting this hypothesis was reviewed. Data from pharmacological studies, mainly in animals, suggest that the actions of both major classes of antidepressant drugs are mediated through the catecholamines. The monoamine oxidase inhibitors increase brain concentrations of norepinephrine while imipramine-like agents potentiate the physiological effects of norepinephrine. Reserpine, a drug which can cause clinical depression, depletes catecholamines, but other amines may also be involved in its mechanism of action. A rigorous extrapolation from pharmacological studies to pathophysiology clearly cannot be made. Clinical studies relevant to the catecholamime hypothesis are limited and the ...

Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system.

Abstract: The effect of L-DOPA and the dopamine (DA) receptor stimulating drug apomorphine was studied in rats after unilateral degeneration of the nigrostriatal DA system by intracerebral injection of 6-hydroxydopamine. Both apomorphine and L-DOPA induced a strong rotational behaviour which was registered in a specially designed “rotameter”. The direction of the rotation indicated that the denervated striatum was more sensitive to DA receptor stimulating drugs than the innervated striatum. This supersensitivity probably corresponded to the decentralisation type of supersensitivity in the peripheral nervous system although it developed faster. The action of L-DOPA was inhibited by pretreatment with the DOPA-decarboxylase inhibitor Ro4–4602 which indicated that L-DOPA must be converted to DA in order to stimulate the supersensitive postsynaptic cells. Pretreatment with a single dose of reserpine also induced supersentitivity to apomorphine which reached its maximum on the 3rd day and then decreased on the 4th day. Postsynaptic supersensitivity after degeneration of the nigro-striatal DA system is probably an important reason for the effectiveness of the L-DOPA therapy against Parkinson's disease.

p-CHLOROPHENYLALANINE: A SPECIFIC DEPLETOR OF BRAIN SEROTONIN

Abstract: p -Chlorophenylalanine has been found to be a potent and selective depletor of brain serotonin (5HT) in mice, rats and dogs. Brain 5-hydroxy-3-indolylacetic acid (5HIAA) content was also depleted by the drug, but catecholamine concentrations were only slightly decreased. Peripheral stores of 5HT were also lowered. In rats, p -chlorophenylalanine reduced the normal increase in brain 5-hydroxyl-3-indolyl compounds following L-tryptophan loading (without apparently affecting tryptophan uptake into brain), completely prevented the increase in brain 5HT accompanying inhibition of monoamine oxidase by pargyline and blocked the increase in brain 5HIAA usually observed after reserpine treatment. p -Chlorophenylalanine slightly diminished the usual increase in brain 5HT in rats following 5-hydroxytryptophan (5HTP) administration, but decreased the rate of disappearance of excess 5HT and antagonized the increase in brain 5HIAA. p -Chlorophenylalanine did not inhibit monoamine oxidase or 5HTP-decarboxylase in vitro and exerted no effect on monoamine oxidase or 5HTP decarboxylase activity of rat tissues in vivo. In contrast, p -chlorophenylalanine inhibited liver tryptophan hydroxylase in vitro and strongly suppressed the tryptophan- and phenylalanine-hydroxylating capabilities of livers of rats treated with it. These results suggest that p -chlorophenylalanine may effect 5HT depletion by inhibiting the biosynthesis of this monoamine, possibly by blocking tryptophan hydroxylation. A blockade of uptake of amino acid precursor might also contribute to the effect of decreasing 5HT biosynthesis. The slow depletion (2-3 days) of brain 5HT induced by p -chlorophenylalanine suggests that an active metabolite might be formed. p -Chlorophenylpyruvic acid exerted essentially the same pharmacologic effects as the amino acid, but it cannot be ascertained at present whether it is the active metabolite because of the interconversion of α-amino acids and α-keto acids in vivo. p -Chlorophenethylamine may be excluded as the metabolite responsible for the action of p -chlorophenylalanine because of the brief duration of the amine in brain and the short lasting, nonselective decrease of both 5HT and norepinephrine produced by the amine. A study of structural variation in the phenylalanine series indicated a specific requirement of a single chlorine substituent in the para position for potent in vivo activity. Rats treated with p -chlorophenylalanine displayed few apparent signs, and certainly not sedation. p -Chlorophenylalanine did not block characteristic signs elicited by reserpine or tetrabenazine in rats. Accordingly, the central actions of reserpine and reserpine-like drugs may possibly be dissociated from both 5HT concentrations and the formation of new 5HT in brain.

3,4-Dihydroxyphenylalanine and 5-Hydroxytryptophan as Reserpine Antagonists

Abstract: THE depletion by reserpine of storage in the body of 5-hydroxytryptamine (‘Serotonin’) and of the catechol amines is now well established1–3. In reserpinized animals the peripheral part of the adrenergic system does not function owing to lack of the transmitter2. This is presumably true also of the central part of the adrenergic system. However, it remains to be proved to what extent the central action of reserpine may be attributed to changes in brain catechol amines and/or 5-hydroxytryptamine.

Norepinephrine in Depressive Reactions: A Review

Abstract: Introduction LITTLE IS known about the possible etiological biochemical factors relating to depressive reactions. Clinical evidence suggests that many depressions respond to the following somatic treatment: electric convulsive therapy (ECT), the imipramine type of drugs, and the monoamine oxidase inhibitor group of drugs. 2,3 Do these two classes of drugs have common factors in their mechanism of action and can this be related to the fact that one antihypertensive agent, namely, reserpine, produces severe depression in a small but consistent number of hypertensive patients? 4-8 Rosenblatt et al, 9 in 1959, were among the first to specifically suggest that changes in brain norepinephrine (NEP) may be involved in depression. Based in part on the knowledge of the effect of reserpine and monoamine oxidase inhibitors on depressed mood and norepinephrine (NEP), they hypothesized that the depressive state might be associated with a relative decrease of norepinephrine