Catecholamines depletion

MTX caused a contraction of vascular smooth muscle and positive inotropic, positive chronotropic and arrhythmogenic effects on cardiac muscle. The effect of MTX was little affected by various receptor blockers, a Na channel blocker or a catecholamine depleting agent. Further, MTX had no effect on the enzymes which were related to Ca movements, such as Na , K -ATPase, cyclic AMP phosphodiesterase, and sarcoplasmic reticulum Ca -ATPase. These results would eliminate the possible involvement of an indirect action elicited by the release of chemical mediators and direct modifications of their receptors, Na channels, or various enzymes as a major mechanism of action of MTX. 

Delgado, PL, Miller, HE, Salomon, RM, Licinio, J, Heninger, GR, Gelenberg, AJ and Charney, DS (1993) Monoamines and the mechanism of antidepressant action effects of catecholamine depletion on mood of patients treated with antidepressants. Psychopharmacol. Bull. 29 389-396. 

Drugs used in the treatment of hypertension vary greatly in their mode of interference with sympathetic nerve function. In the case of methyldopa the mechanism is complex and still largely unknown. Others, such as guanoxan, guanochlororbethanidine, involve varying degrees of, for example catecholamine depletion, blockade of subsequent release of noradrenaline and, occasionally, a weak receptor-blockade. Bethanidine is perhaps the best-known of this series and... 

Drugs that may be affected by carvedilol include antidiabetic agents, calcium blockers, clonidine, cyclosporine, disopyramide, catecholamine depleting agents (eg, reserpine), and digoxin. 

Ophthalmic beta blockers may affect oral beta blockers, catecholamine-depleting drugs, calcium antagonists, digitalis, and phenothiazines. 

Drugs that may affect ophthalmic beta blockers include catecholamine-depleting drugs, digitalis, and quinidine. 

The neurochemical needs of the PEC have been studied more intensively than other cortical areas because of the immediate relevance of this cortical area to neuropsychiatry and the pioneering work of Brozoski et ak (1979), who found dramatic effects of catecholamine depletion in PFC. The following represents a brief summary of this field. For more detailed reviews of this topic, see Arnsten (1998), Robbins et ak (1998), Sarter and Bruno (2000), and Arnsten and Robbins (2002). 

Migliorelli R, Starkstein SE, Teson A, et al SPECT findings in patients with primary mania. J Neuropsychiatry Chn Neurosci 5 379-383, 1993 Miller HE, Delgado PL, Salomon RM, et al Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. Arch Gen Psychiatry 53 117-128, 1996a... 

Guanethidine, rarely used as a hypotensive drug, also causes some catecholamine depletion, but unlike reserpine it does not cross the blood-brain barrier and thus has no central sedative effects. It acts selectively because it is taken up into the neuron by the same amine pump that transports the neurotransmitter. 

Synthesis inhibitors block tryptophan hydroxylase, the first rate-determining enzyme in serotonin synthesis. Although p-chlorophenylalanine (4.111) can decrease serotonin levels by more than 90%, this agent does not cause the sedation that is seen after catecholamine depletion with reserpine. Therefore, reserpine, although capable of depleting 5-HT vesicles, causes sedation by a catecholaminergic mechanism that inhibits uptake-2. It acts on the membrane of the synaptic vesicle and seems to prevent 5-HT and catecholamine uptake into the granule. 

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. 

Calabresi P, Benedetti M, Mercuri NB, Bernardi G (1988) Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum Intracellular studies from naive and catecholamine-depleted rats. 

Kobayashi K, Morita S, Sawada H, Mizuguchi T, Yamada K, Nagatsu I, Hata T, Watanabe Y, Fujita K, Nagatsu T (1995) Targeted disruption of the tyrosine hydroxylase locus results in severe catecholamine depletion and perinatal lethality in mice. J Biol Chem 270 27235-27243. 

White BC, Tapp WN (1977) Unilateral catecholamine depletion of the corpus striatum and amphetamine-induced turning an ontogenetic study. Psychopharmacology (Berl) 53 211-212. 

Berman RM, Narasimhan M, Miller HL, Anand A, Cappiello A, Oren DA, Heninger GR, Charney DS. Transient depressive relapse induced by catecholamine depletion potential phenotypic vulnerability marker Arch Gen Psychiatry 1999 56(5) 395-403. 

Verhoeff NP, Christensen BK, Hussey D, Lee M, Papatheodorou G, Kopala L, Rui Q, Zipursky RB, Kapur S. Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans a rephcation study. Pharmacol Biochem Behav 2003 74(2) 425-32. 

Benzodiazepines - A supraspinal site of action has been demonstrated for chlordiazepoxide and diazepam as well as for meprobamate.88 xhe anticonvulsant action of chlordiazepoxide resembles that of dilantin instead of that of acetazolamide, being antagonized by reserpine but not by 0 -methyl DOPA or Ct-methyltyrosine.89 This antagonistic effect of reserpine is reduced by a-methyl DOPA, serotonin and amphetamine. The reserpine effect is thus obtained by some means other than its catecholamine-depleting action and the anticonvulsant action of chlordiazepoxide is not mediated by catecholamines. 

It should be mentioned that / -chlorophenylalanine (fenclonine) is an irreversible inhibitor of tryptophan hydroxylase, the first and rate-determining step in serotonin synthesis. Even though the efficiency of this decrease in 5HT may be as high as 90%, sedation does not result. Reserpine alkaloids, which also deplete 5HT and NE, are sedative. That leaves catecholamine depletion as relevant to sedation. It is interesting that p-chloropheny-lalanine is used to treat carcinoid syndrome, which is a nonmalignanf intestinal mucosal tumor pouring prodigious amounts of 5HT into the circulation. 

Catecholamine-depleting drugs, such as reserpine and guanethidine, enhance the hypotensive effects of sotalol. Calcium-channel antagonists enhance myocardial... 

Shukla VH, Dave KR, Katyare SS Effect of catecholamine depletion on oxidative energy metabolism in... 

The slower contraction is abolished by phentolamine and reserpine whereas the first contraction remains unaffected. Both phases are inhibited by verapamil or a calcium-free medium but are not affected by atropine, TTX, or chlorpheniramine (adrenoreceptor blockers, sodium channel blockers, catecholamine depleting drugs). 

The adrenal catecholamine content of guinea pigs and rats exposed to 7.5 per cent oxygen in nitrogen for periods of 4, 8, and 12 h decreased significantly (Steinsland et al. 1970). The rate of adrenal catecholamine depletion in hypoxic rats treated with a-methyl-L-tyrosine (100 mg/k i.p.at 5-h interval) followed a patters which reflects an alteration in catecholamine release after 12 h. 

The real picture is considerably more complicated. A number of findings indicate, for example, that norepinephrine depletion only causes a reduction in blood pressure of therapeutic value if it occurs in central neurones. The replacement of norepinephrine by a-methylnorepinephrine in peripheral organs does not bring about any fall in blood pressure [135]. The hypotensive effect of methyldopa and its analogues does not run parallel to the catecholamine depletion caused by these substances in the heart [42]. 

After a study of the cardiac depressant action of KL-255, it was suggested that myocardial depression may be a result of 3-blockade of the basal tone established by endogenously released catecholamines. Catecholamine depletion by guanethidine resulted in a loss of the depression of contractile force normally observed with KL-255. The depressant effects did not appear to be dose-related to local anesthetic action. 

For example, chlorpromazine enhanced central catecholamine biosynthesis vivo by Increasing the hydroxylation of tyro-sinei07 10 Chlorpromazine also accelerated cerebral catecholamine depletion in rats pretreated with a tyrosine hydroxylase inhibitor. The latter experiments using hlstochemical... 

The antihypertensive effects of a-methylated catecholamine analogs have been studied.In renal hypertensive rats, prolonged treatment with a-methyldopa, a-methyl- m-tyrosine, a-meth-yltyrosine or metaraminol produces dose-dependent decreases in blood pressure and dose-dependent depletion of myocardial catecholamines. The same order of relative activities was found in regard to noradrenaline depletion and antihypertensive effect, but there was no relationship between the degree of catecholamine depletion and the intensity of the hypotensive effect. 

Frontali, N., 1972. Catecholamine-depleting effect of black widow spider venom on iris nerve fibers. Brain Res. 37 146-148. 

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