Reserpine Monoamine oxidase inhibitors

PscHEiDT, G. R. and Himwich, H. E., Reserpine, monoamine oxidase inhibitors, and distribution of biogenic amines in monkey brain, Biochem, Pharmacol 12, 65 (1963). 

Levodopa interacts with many different drugs. When levodopa is used with phenytoin, reserpine, and papaverine, there is a decrease in response to levodopa The risk of a hypertensive crisis increases when levodopa is used with the monoamine oxidase inhibitors (see Chap. 31). Foods high in pyridoxine (vitamin B6) or vitamin B6 preparations reverse the effect of levodopa However, when carbidopa is used with levodopa, pyridoxine has no effect on the action of levodopa hi fact, when levodopa and carbidopa are given together, pyridoxine may be prescribed to decrease the adverse effects associated with levodopa... 

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. 

Among methoxy-substituted yohimbine alkaloids, only 11-methoxy-a-yohim-bine (95) and 1 l-methoxy-3-epi-a-yohimbine (106) were tested for a-adrenergic activity, and they showed only weak a2-adrenoceptor blocking effect (347). On the other hand, venenatine (107) has reserpinelike activity and shows synergism with reserpine (109). Furthermore, alstovenine (96) displays monoamine oxidase inhibitor activity (348). 

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Development of sexual behavior can be affected by neonatal pharmacological treatment with the monoamine oxidase inhibitor pargyline, the monoamine depletor reserpine as well as with the acetylcholine esterase inhibitor pyridostigmine. These results suggest that biogenic amines are involved in sexual differentiation of the brain (refs. 162, 163). Pargyline treatment from day 1 to 14 or day 15 to 28 resulted in earlier development of puberty in female rats and delayed appearance of puberty in male rats. Male sexual behavior was decreased in both sexes. Treatment with reserpine on days 1, 4, 7 and 10 delayed the manifestation of puberty in both sexes, and caused disturbed female ovarian cycles and decreased male mounting behavior. 

These pranises have so far been established as true for extremely few ugs. In some cases, they monoamine-oxidase inhibitors) or by depletion of stored materials (e.g. reserpine) belong in this category. 

Patients taking monoamine oxidase inhibitors, anticholinergic drugs (such as tricyclic antidepressants), propranolol, reserpine, guanethidine, and methyldopa should be monitored closely if phenylephrine is used (SEDA-16, 542) (16). 

Antidepressants (tricyclics, monoamine oxidase inhibitors) Antihypertensives (calcium channel blockers, methyidopa, reserpine)... 

The most characteristic (but not completely specific ) pharmacological action of the monoamine oxidase inhibitors is their ability to reverse reserpine sedation and to potentiate the excitatory effects of 5-hydroxtryptamine administration . Given alone, in single doses, they produce no obvious hyperactivity in experimental animals and they may even cause depression. After prolonged administration, sympathetic stimulation and locomotor hyperactivity do occur but these actions are still not so marked as when the inhibitors are administered in conjunction with 5-HTP. The physiological significance of this observation has been discussed earlier (p. 269). 

Although the available evidence suggests that the antidepressant action of the monoamine oxidase inhibitors stems from their ability to increase the amount of noradrenaline in the brain, it should be remembered that many other compounds, including some depressants, also possess some ability to inhibit monoamine oxidase. Moreover, orally administered DOPA which, like the enzyme inhibitors, should also increase both the dopamine and the noradrenaline content of brain, is quite ineffective in relieving depression , though, as pointed out earlier, it does reverse sedation due to reserpine. Even if the effects of monoamine oxidase inhibitors are the consequence of... 

Reserpine depletes the brain of dopamine and it is interesting that it produces only a slight increase in extrapyramidal symptoms in cases of severe Parkinsonism although it retains its tranquillizing activity . There is evidence also that, as in reserpinized animals, monoamine oxidase inhibitors do not increase the amount of dopamine in the brain of Parkinsonian patients, though accumulation of noradrenaline does occur. This has led some to suggest that in Parkinson s disease there is a reserpine-like principle in brain which interferes with the storage of dopamine. 

Reserpine is long-acting, and the postsynaptic neurons respond to the paucity of norepinephrine by "upregulating" (increasing) the number of receptors on the postsynaptic membrane. As a result, the postsynaptic terminal is supersensitive to direct sympathomi-metics. Consequently monoamine oxidase inhibitors (which prevent destruction of endogenous catecholamines such as norepinephrine and epinephrine) and direct sympathomimetics (Table 2.1 A) should be avoided in patients who have received reserpine. 

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