Reserpine syndrome

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. 

Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i.e. 6-OHDA and MPTP, it should be possible to produce appropriate experimental models. Certainly both toxins cause rotational behaviour in rats (Fig. 7.7) but no rodent shows a syndrome suggestive of PD. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation. Reserpine causes a depletion of all brain monoamines and produces motor defects in rats, which, even if not PD-like, do respond to DA manipulation. 

A 5-HTlA receptor agonist will be identified in this model as a compound which induces the 5-HT behavioural syndrome (fiat body posture, abducted hind and forelegs and forepaw treading). In addition, an a-adren-ergic agonist induces piloerection in the reserpinized rat. 

Hermoni M, Lerer B, Ebstein RP, et al Chronic lithium prevents reserpine-induced supersensitivity of adenylate cyclase. J Pharm Pharmacol 32 510-511, 1980 Hertzman PA, Blevins WL, Mayer J, et al Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan [see comments]. N Engl J Med 322 869-873, 1990... 

The behavioral syndrome induced in mice and rats by reserpine sedation, catalepsy and ptosis can be reversed by imipramine. 

Conditions mimicking MDD can occur secondary to a wide variety of prescribed and illicit agents. With some drugs, the syndrome occurs as a direct and immediate effect. For example, some antihypertensive agents (e.g., reserpine, a-methyidopa) acutely antagonize central biogenic amine neurotransmitter systems. 

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... 

It potentiates (already in low doses) the excitement syndrome induced by DOPA and simultaneously annihilates the depression caused by reserpine. In man, 74 seems to be useful in the treatment of psychoses and schizophrenia. 

The Rauwolfia alkaloids, including reserpine, are now little used. They act by depleting neurotransmitter stores of catecholamines and reducing sympathetic nervous activity, but their effects are non-specific, and nervous system adverse effects (depression, drowsiness, tiredness, confusion) are prominent. There is also a troublesome incidence of diarrhea, hjrperprolactinemia, gynecomastia, and a possible withdrawal syndrome. 

Different distribution characteristics were also observed39 for dopamine (5) and its tris(trimethylsilyl) and tetrakis(trimethylsilyl) derivatives 6 and 7, respectively. In contrast to 5, for which the blood-brain barrier is nearly impermeable, the much more lipophilic silyl derivatives 6 and 7 were found to exhibit central effects when given intraperitoneally to rats. At a dosage of 100 mg per kg, they influence positively the rigid akinetic syndrom, which was induced by reserpine. These results may be explained in terms of a pro-drug behavior of 6 and 7. (In this context see also Reference 40.)... 

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. 

SLC18 Vesicular amine transporter 3 Reserpine Myasthenic syndromes... 

Procyclidine being a structurally similar chemical congener of trihexyphenidyl possesses also similar properties. It is used for the symptomatic treatment ofpostencephalitic parkinsonism. It has also been employed successfully to alleviate the extrapyramidal syndrome induced by such drugs as reserpine andphenothiazine analogues. 

It is employed in the symptomatie eontrol and management of Parkinson s disease. It has also been used in the treatment of acute spastic disorders of the skeletal muscles caused hy trauma, tension, and vertebral disk dislocation. It is also used alleviate the extrapyramidal syndrome induced by drugs, e.g., reserpine and phenothiazine derivatives. 

Furthermore, both methyldopa and reserpine, that essentially interfere with the catecholamine synthesis as well as its storage, exacerbate the Parkinson syndrome and, therefore, antagonize the activity of levodopa. The pharmacological profile of levodopa actually synergized by antimuscarinics. 

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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