Subject Reserpine

Results of studies on the role of serotonin-in the action of LSD, which were conducted on human subjects, may be more easily interpreted because they directly examined the hallucinogenic effects of LSD. Prior depletion of brain serotonin with reserpine accentuated the effects of LSD (34,71). As described above, prior treatment with a MAOI attenuated the effects of LSD (38,70) and... 

Resnick, O., Krus, D. M., and Raskin, M. (1965) Accentuation of the psychological effects of LSD-25 in normal subjects treated with reserpine. Life Sci., 4 1433-1437. 

Reserpine, an alkaloid from the Rauwolfia plant, abolishes the vesicular storage of biogenic amines (NE, dopamine = DA, serotonin = 5-HT) by inhibiting an ATPase required for the vesicular amine pump. The amount of NE re-Liillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

The results with methylphenidate, however, are more impressive. Two of three studies found a significant effect and the third found improvement on the patients subjective evaluation. Although amphetamine and methylphenidate are similar in their pharmacology, they differ in some respects. Amphetamine releases dopamine from newly synthesized pools (a-methyl-p-tyrosine-sensitive pool) whereas methylphenidate releases dopamine from storage sites (reserpine-sensitive sites). This pharmacological difference could be related to the apparent greater efficacy of methylphenidate. 

In the total synthesis of reserpine, Woodward and collaborators (10) have reported that the quaternary iminium salt J8 was reduced with aqueous metha-nolic sodium borohydride to methyl 0-acetyl isoreserpate 09). This is the anticipated product whether the stereochemical sense of the reaction is subject to steric or thermodynamic control as pointed out by Woodward. It is also the expected one on the basis of stereoelectronic control. 

Reserpine, an alkaloid from the climbing shrub Rauwolfm serpentina (native to the Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Esterification of the 18-hydroxyl followed by an acid-catalyzed equilibration (at C-3, cf. isoreserpine reserpine) resulted in the formation and isolation of the inverted equivalent of reserpine (XVIII). The conversion into the reserpine configuration requires a comment, since it is probably facilitated in this case by an adverse interaction in the trans-trans-cis form between the C-9 proton and the methylene group at C-14. Congeners of reserpine were also subjected to this sequence of... 

Hydrochlorothiazide can be separated from reserpine and hydralazine using ion-exchange column chromatography. A solution of known concentration is then subjected to analysis by UV spectroscopy and compared to a standard solution. The quantity of hydrochlorothiazide present in the sample is then determined. 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

Finally, it should be recalled that DOPA can itself produce extrapyramidal effects as well as reversing them , that reserpine can reverse tremorine induced tremor in rats as well as producing Parkinsonian side effects in the human subject and that, many years ago, bulbocapnine was used in the treatment of Parkinson s disease. 

The monoterpenoid-derived alkaloid reserpine (XLV, Fig. 3), the history and pharmacology of which have been the subjects of numerous reviews [251 to 254, 958-969], can be regarded as a structurally specific agent, both on account of the specific nature of its sedative action and because the bewildering complexity of its overall effects probably [969] resides simply in its ability to procure the release of monoamines from their storage sites, both central and peripheral - just as the complex actions of nicotine stem primarily from its action on the ganglia. The structurally specific nature of reserpine would also be borne... 

Reserpine, tritiated in the 2-and 6-positions of the trimethoxy-benzoyl ring, was administered orally to human subjects. The major urin u y metabolite was H-trimethoxybenzoic acid, while most of the radioactivity in the feces, the predominant route of excretion, was unaltered reserpine. ... 

The antidepressant activity of hypericum has been extensively investigated over the last two decades in animal models (forced-swimming and tail-suspension tests) as well as in humans. Clinical trials have demonstrated an improvement in symptoms of anxiety, dysphoric mood, hypersomnia, anorexia, depression, insomnia, psychomotor retardation, and other subjective indicators.Potential for the treatment of premenstrual syndrome (PMS) also exists. Earlier studies also showed that hypericum enhanced mice exploratory activity in a foreign environment, extended narcotic sleeping time (dose dependent), is a reserpine antagonist, and decreased aggression in socially isolated male mice. Hypericin has been found to inhibit in vitro almost irreversibly both type A and B monoamine oxidase (MAO) in rat brain mitochondria. Type A MAO (serotonin) inhibition was more pronounced, but with long-term use (8 weeks of daily treatment). Other mechanisms of action, such as serotonin transport and up-... 

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