Reserpine MAOIs

Iproniazid also prevents the reserpine syndrome in rats. Reserpine blocks vesicular uptake of monoamines which, as a consequence, leak from the storage vesicles into the cytosol. Although these monoamines would normally be metabolised by MAO, they are conserved when a MAO inhibitor (MAOI) is present, and so co-administration of reserpine and a MAOI leads to accumulation of monoamines in the neuronal cytosol. It is now known that, when the concentration of cytoplasmic monoamines is increased in this way, they are exported to the synapse on membrane-bound monoamine transporters. The ensuing increase in monoamine transmission, despite the depletion of the vesicular pool, presumably accounts for the effects of iproniazid on the behaviour of reserpine-pretreated rats. 

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... 

Pseudoephedrine (Sudafed, Novafed, Afrinol, Others) [OTC] [Decongestant/Sympothomimetic] Uses Deconge tant Action Stimulates a-adren gic rec tors w/ vasoconstriction Dose Adults. 30-60 mg PO q6—8h Peds. 4 mg/kg/24 h PO qid -1- in renal insuff Caution [C, +] Contra Poorly controlled HTN or CAD, w/MAOIs Disp Tabs, caps, Liq SE HTN, insomnia, tach, arrhythmias, nervousness, tremor Interactions T Risk of HTN crisis W/ MAOIs T effects W/BBs, sympathomimetics X effects W/TCAs -1- effect OF methyldopa, reserpine EMS Found in many OTC cough/cold pr >arations use sympathomimetics w/ caution, may T adverse effects OD May cause N/V, HTN, arrhythmias, and Szs symptomatic and supportive... 

Paralleling these clinical developments were basic pharmacological studies, which noted that reserpine ( 5, 6, 7 and 8) and a-methyidopa produced depression in patients treated for hypertension ( 9,10 and 11). The fact that the MAOIs and TCAs functionally increased norepinephrine (NE) activity while reserpine lowered its activity led Schiidkraut (12) and Bunney and Davis (13) to independently formulate the NE hypothesis of depression. This same line of reasoning was also applied to serotonin (5-HT) (14, 15). 

Most antihistamines possess anticholinergic properties that by themselves are of minor intensity but may increase considerably if given together with MAOIs. Interactions of MAOIs with antihypertensives (e.g., reserpine-type drugs) and oral antidiabetic drugs, as well as insulin and L-dopa, have all been encountered. It can be seen why MAO inhibitors are not viewed today as initial therapy except possibly in atypical depression. Certain panic and phobic reactions respond well. An important indication would be in case of therapeutic failures with the tricyclic or other heterocyclic antidepressants. 

A prolonged period of increased motor activity after starting reserpine ( reserpine-reversal ) possibly occurred in 3 patients with schizophrenia treated firstly with phenelzine for 12 weeks, then a placebo for 16 to 33 weeks, and lastly reserpine for 12 weeks, when compared with patients receiving reserpine who had not received an MAOI. Their blood pressures rose slightly and persistently, and their psychomotor activity was considerably increased, lasting in two cases throughout the 12-week period of treatment. ... 

Theoretically, reserpine might cause hypertension in patients treated with non-selective MAOIs (see Mechanism). On the basis of this the US manufacturer of tranylcypromine contraindicates concurrent use. Conversely, the UK manufacturer of isocarboxazid mentions that it may potentiate the hypotensive effect of reserpine (MAOIs alone can have hypotensive effects). 

MAOI counteract the pharmacological effects of drugs such as reserpine. They influence carbohydrate metabolism since blood lactate and pyruvate levels are increased. Most biochemical and pharmacological effects of MAOI. as measured by their intensity, onset, duration of action and nature, depend largely on the species, the tissue, the amine studied, the mode of administration and the drug pharmacokinetics, which make it almost impossible to predict accurately their action. 

Reserpine treatment of human subjects may lead to various reversible parkinsonian symptoms and rats given the drug also exhibit akinesia, tremor and rigidity [220, 221]. Symptoms in animals appear to be related to the brain amine depleting effect of reserpine as they were reversed by intravenous L-dopa and L-5HTP but not by DA and 5HT which do not penetrate to the brain [222]. That they are due specifically to a striatal DA decrease is consistent with the absence of reversal by MAOI + dihydroxyphenylserine [223] (a precursor of NA but not of DA) but appear to be contradicted by reversal with 5HTP. Furthermore, reserpine caused akinesia even when given to rabbits from which the caudate nuclei had been removed [224]. 

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