Reserpine interaction

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. 

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... 

A second, more extensive experiment involved oral administration of three daily doses (100 mg/kg) of parachlorophenylalanine (PCPA). This tryptophan hydroxylase inhibitor (47), like reserpine, enhanced the behavioral effects of LSD (13) moreover, hypersensitivity occurred when 5-HT, but not other monoamine, concentrations were below normal in both forebrain and hindbrain (13). That is, effects were observed at 5 and 12 days (when 5-HT was depleted to 10-20% and 60-70% of normal) but not at 21 days (when 5-HT had returned to normal). Control experiments (13) indicated that (a) the interaction of PCPA, 5-HT, and LSD was probably not caused by generalized hyperactivity or hyperirritability sometimes seen after PCPA (73) (b) PCPA does not affect threshold doses of other psychoactive but nonserotonergic compounds, such as d-amphetamine (0.3 mg/kg) and (c) pretreatment with a-methylparatyrosine, a tyrosine hydroxylase inhibitor which depletes catecholamines rather than indoleamines, does not alter sensitivity to LSD. 

Finally, it is worth mentioning that 15N-NMR spectra of yohimbine (74), reserpine (109), and isoreserpine (514) also have been investigated (319). The 15N chemical-shift differences between C/D-cis- and trans-fused compounds could be explained by a hyperconjugative interaction between the antiperiplanar C—H bonds and the nitrogen lone pair characteristic for trans-fused compounds only. 

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... 

Other drug effects that decrease DA activity also support this position. Thus, when DA synthesis is blocked by a-methyl- p-tyrosine (AMPT), the dose necessary for an antipsychotic effect is reduced (i.e., the dose-response curve is shifted to the left by the interaction between dopamine and AMPT). A drug such as reserpine that can deplete DA stores also has relatively mild antipsychotic properties. Also, aripiprazole, which has D 2 presynaptic agonist properties, decreases the production of DA, as well as blocking D2 postsynaptic receptors. 

This phenomenon is one of the pillars of the biogenic amine hypothesis of depression (see Suicide later in this chapter). An intriguing finding with reserpine is that those susceptible to a depressive syndrome while on this agent also have an increased likelihood of a personal or family history of MDD, in comparison with those who are not susceptible. This finding suggests an interaction between a constitutional predisposition and the biochemical effects of this drug. Because depression is a... 

So far we have treated activation and modulation as separate processes. We will want to preserve that distinction even now as we explore their close interaction. In mania, whether it be driven by stimulants or by high levels of endogenous aminergic neuromodulator, the activation level is raised and the tendency to sleep is lowered. In depression, whether it comes in response to amine depletion by drugs like reserpine or to low levels of endogenous neuromodulators, the activation level is always low and the tendency to sleep may be high. There are notable exceptions to these rules, especially in depression, which is sometimes associated with extreme motor agitation and severe insomnia. 

WARNING Exacerbation of ischemic heart Dz w/ abrupt D/C Uses HTN MI Action [3-Adrenergic receptor blocker, 3ls fi2 Dose HTN 10-20 mg bid, up to 60 mg/d MI 10 mg bid Caution [C (1st tri D if 2nd or 3rd tri), +] Contra CHF, cardiogenic shock, bradycardia, heart block, COPD, asthma Disp Tabs SE Sexual dysfxn, arrhythmia, dizziness, fatigue, CHF Interactions T Effects W/ antihypertensives, ciprofloxacin, fentanyl, nitrates, quinidine, reserpine T bradycardia and... 

Drug interactions Catecholamine-depleting drugs such as reserpine may have an additive effect in combination with betablockers. Drugs that inhibit CYP2D6 (quinidine, fluoxetine, paroxetine, and propafenone) increase metoprolol concentration. 

Costa, E., Garattini, S., StValzelli, L. 1960, Interactions between reserpine, chlor-promazine, and imipramine, Experientia, vol. 16, pp. 461-463. 

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... 

Interactions of sympathomimetics with other vasoactive drugs are complex. Some drugs block the reuptake mechanism for noradrenaline in adrenergic nerve terminals and potentiate the pressor effects of noradrenaline e.g. cocaine, tricyclic antidepressants or highly noradrenaline-selective reuptake inhibitors such as roboxetine. Others deplete or destroy the intracellular stores within adrenergic nerve terminals (e.g. reserpine and guanethidine) and thus block the action of indirect S5unpathomimetics. 

Clinically important, potentially hazardous interactions with beta-blockers, calcium channel blockers, reserpine... 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

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