Reserpine depression

Central neuronal blockers (reserpine) Depression, sedation, nasal congestion... 

Contraindications Orthostatic hypotension, liver disease Orthostatic hypotension Asthma, heart block Volume depletion Pregnancy Orthostatic hypotension Pheochromocytoma. Reserpine depression. Guanethidine CHF. ... 

Brodie demonstrated that the tricyclic antidepressants do not reverse reserpine depression if the animal has been depleted of both dopamine and NE hence, he concluded that their action depends on the presence... 

Sitosterol 3-(5-D-glucoside Ficus religiosa 0/ Moraceae Bark It reportedly showed hypoglycemic activity in rabbits, which reached a maximum after 4 hours when the compound was administered orally at 25 mg/kg and after 2 hour when the compound was administered i.v. at 5 and 7.5 mg/kg. It produced CNS stimulation, convulsions and reversal of reserpine depression in mice at toxic dose levels. I.D50 was found to be 62 mg/ kg in mice [45],... 

In a series of analogues (53) showed a pronounced antidepressant profile. It counteracted reserpine (depression in mice and emesis in pigeons) and potentiated the action of amphetamine. The position of the alkanoyl residue seemed to be very specific. Small variations of the propionyl moiety abolished the antidepressant activity and (in some cases) gave other effects e.g. depressive with Et CHOH- and hypotensive with EtSOi- [156]. Compound (53) was well tolerated and showed no particularly adverse effect in humans in a 4-wk study at 40-80 mg daily. Ginical studies in patients have been started [157]. 

VMATs are irreversibly inhibited by the potent antihypertensive drug reserpine. The depressive effects of reserpine helped to formulate the original monoamine hypothesis of affective disorders. Reseipine also appears to interact with the transporters near the site of substrate recognition. Tetrabenazine, which is used in treatment of movement disorders, inhibits VMAT2 much more potently than VMAT1, consistent with the less hypotensive action of this agent. 

A link between the central monoamines, 5-hydroxytryptamine (5-HT) and noradrenaline, and depression was forged some 40 years ago and arose from clinical experience with the drugs, reserpine and iproniazid. At that time, reserpine was used as an... 

Other Agents Reserpine No recommendations at this time Mental depression May be used in resistant hypertension when combined with a thiazide... 

But that was only one half of the logic behind the chemical-imbalance theory. The other half came from studies of reserpine, a drug that was extracted from Rauvolfia serpentina or the Indian snakeroot plant, which had historically been used to treat snakebite, hypertension, insomnia and insanity. In studies of animals, reserpine was reported to induce sedation and to decrease brain levels of norepinephrine, serotonin and dopamine. Clinical reports indicated that some people became severely depressed when taking reserpine.14 Putting these two findings together, it seemed likely that reserpine made people depressed because it decreased neurotransmitter levels. 

When the reserpine studies are added to the antidepressant studies, the logic behind the chemical-imbalance theory begins to look compelling. Drugs like reserpine that decrease monoamine neurotransmitters make people depressed. Drugs that increase these neurotransmitters by one means or another relieve their depression. Hence, depression is due to a monoamine deficiency. 

Part of the initial argument for the chemical-imbalance hypothesis was that reserpine supposedly decreases the availability of monoamines and thereby makes people depressed. But does it ... 

Like the articles indicating that iproniazid and imipramine functioned as antidepressants, the conclusion that reserpine makes people depressed was based on clinical reports, rather than controlled trials. 

The re-examination of the clinical reports showing that most people who were given reserpine did not become depressed was not published until 1971, a few years after the chemical-imbalance theory had been popularized by Schildkraut and Coppen. But a decade before their influential articles were written, there had been a carefully controlled clinical trial on the effects of reserpine on mood.17 Far from confirming the belief that it made people depressed, the study seemed to show the reverse. Rather than making healthy people depressed, reserpine seemed to make depressed people better. As described by Michael Shepherd, the senior author of the study, in 1956 ... 

When we began using reserpine at the Maudsley Hospital less than two years ago there were very few reliable accounts of its use in the treatment of neuropsychiatric conditions and almost no controlled clinical studies. Dr D. L. Davies and I therefore conducted a clinical trial on a mixed group of out-patients, the majority of whom were suffering from anxiety and depressive reactions. The patients were given either reserpine, prescribed as Serpasil in a dose of 0.5 mg. by mouth twice daily, or a seemingly identical placebo, for a period of six weeks. The two substances... 

When Schildkraut introduced the monoamine theory of depression, he admitted that there was little direct evidence for it. Instead, it was based on the supposed effectiveness of antidepressant medication and the mistaken belief that reserpine makes people depressed. Schildkraut acknowledged that Most of this evidence is indirect, deriving from pharmacological studies with drugs such as reserpine, amphetamine and the monoamine oxidase inhibitor antidepressants which produce affective changes. 21 A half-century has passed since his chemical-imbalance theory of depression was introduced, and the presumed effectiveness of antidepressants remains the primary evidence in its support. But as we have seen, the therapeutic effects of antidepressants are largely due to the placebo effect, and this pretty much knocks the legs out from under the biochemical theory. 

There are a few substances that can reduce serotonin, norepinephrine and/or dopamine rapidly and substantially, reducing them to levels thought to be lower than those of depressed patients.23 That is what reserpine was supposed to do and, as we have seen, it did not cause depression - despite the early clinical impression that it did. Other substances have been used in later studies, the most common of which are amino-acid mixtures that lack the essential amino acids needed by the body to produce these neurotransmitters. For example, having people drink a beverage that is rich in amino acids, but does not contain tryptophan (the amino acid needed to produce serotonin), lowers their serotonin levels within a couple of hours. 

Daniels, A. M. and R. Sallie, Headache, Lumbar Puncture, and Expectation , The Lancet 1, no. 8227 (1981) 1003 Davanloo, H., Basic Principles and Techniques in Short-Term Depression, New York S. P. Medical 8C Scientific Books, 1976 Davies, D. L. and Michael Shepherd, Reserpine in the Treatment of Anxious and Depressed Patients , The Lancet 266, no. 6881 (1955) 117-20 Davies, Sharon, Potential Conflicts of Interest More Information from Jama , British Medical Journal (2009) http / / www.bmj.com/cgi/elet-ters / 338 / feb 05 i / b463... 

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

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