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PubMed2004

(-)-Amarbellisine, a lycorine-type alkaloid from Amaryllis belladonna L. growing in Egypt.

A new lycorine-type alkaloid, named (-)-amarbellisine, was isolated from the bulbs of Egyptian Amaryllis belladonna L. together with the well known alkaloids (-)-lycorine, (-)-pancracine, (+)-vittatine, (+)-11-hydroxyvittatine, and (+)-hippeastrine. The new alkaloid, containing the pyrrolo[de]phenanthridine ring system, was essentially characterised by spectroscopic and optical methods, and proved to be the 2-methoxy-3a,4,5,7,11b,11c-hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridinol. By using HPTLC technique we also carried out a comparative study of the relative and total alkaloidal content at two different stages of plant growth. Finally, the antimicrobial activity of the isolated alkaloids was assayed.

Amaryllidaceae Alkaloids↗
PubMed2003

Beans, roots and leaves: a brief history of the pharmacological therapy of parkinsonism.

It is not clear whether parkinsonism as it is now defined - a progressive neurodegenerative disorder of the basal ganglia characterized by sharply reduced striatal dopamine levels - has always affected a significant minority of aged persons, but suggestive evidence to this effect is reviewed. THe major discussion commences, however, with the administration of various plant alkaloids to parkinsonism patients in the second half of the 19th century. Antiparkinsonian therapy since this time can be divided into a number of phases: 1. Employment of alkaloids derived from solanaceous plants: initially hyoscyamine, then hyoscien/scopolamine. 2. With the outbreak of encephalitis lethargica during the First World War, parkinsonian patient numbers increased dramatically, leading to a multiplicity of new directions, including high dose atropine and harmala alkaloid therapies. 3. The "Bulgarian treatment", popularized in western Europe in the mid-1930s, was also a belladona alkaloid-based therapy, but associated with greater efficacy and few side effects. This approach, whether as actual plant extracts or as defined combinations of belladona alkaloids, remained internationally dominant until the end of the 1940s. 4. Following the Second World War, synthetic antiparkinsonism agents were developed with the aim of overcoming the deficiencies of belladonna alkaloid therapy. These agents fell into two major classes: synthetic anticholinergic agents, such as benzhexol, and antihistaminergic drugs, including diphenhydramine. 5. A complete change in direction was heralded by the discovery in 1960 of the striatal dopamine deficit in parkinsonism. This led to the introduction of L-DOPA therapy, the first approach directed against an identified physiological abnormality in the disorder. 6. Subsequent developments have thus far refined of supplemented the L-DOPA effect. Recent attempts to develop neuroprotective or -restorative approaches are also briefly discussed. The history of antiparkinsonian therapy illustrates the fact that the nature of experimental clinical pharmacology has markedly changed during the 20th century: No longer the preserve of individual physicians, it is now based firmly on fundamental laboratory research, the clinical relevance of which is not always immediately apparent, and which is only later examined in clinical trials. It is nonetheless concluded that antiparkinsonian therapy was never 'irrational', but has always been necessarily rooted in current knowledge regarding neural and muscular function. The achievements of L-DOPA therapy, the first successful pharmacological treatment for a neurodegenerative disorder, derived from the fruitful union of hte skills and contributions of different types by laboratory scientists, pharmacologists and clinicians.

Drug Therapy↗
PubMed1980

Lack of side effects from topically administered 10% phenylephrine eyedrops. A controlled study.

A prospective double-blind study was designed to determine the systemic hypertensive effects of topically administered 10% aqueous buffered phenylephrine hydrochloride vs topically administered 1% aqueous tropicamide, a belladonna alkaloid devoid of vasopressor effect. One hundred persons received phenylephrine, while 50 persons received tropicamide. One drop of coded drug was administered in both eyes of each patient at two-minute intervals over a four-minute period. Blood pressure and pulse rate were measured immediately prior to drop instillation, and 5, 15, and 30 minutes following instillation of the final set of drops. Mean blood pressure and pulse rate dropped from baseline values in both groups at 5, 15, and 30 minutes after drug administration. There was no statistically significant difference between the experimental and control groups with respect to drug effect on either blood pressure or pulse rate throughout the study.

Adolescent↗
PubMed1976

Analysis of alkaloid mixtures by charge-transfer complexation.

Binary mixtures of weak and strong UV-absorbing alkaloids were analyzed by a charge-transfer spectrophotometric method, utilizing iodine in ethylene dichloride as the acceptor. In the uncomplexed form, the strong absorbing alkaloid (papaverine, quinine, ergotamine, or reserpine) was measured at a wavelength where there was no interference from weak absorbers (at 335, 332, 315, or 300 nm, respectively). The weak absorbing alkaloid (ephedrine, codeine, atropine, or homatropine methylbromide) was determined by computing its contribution to the total charge-transfer band at 295 nm where absorbance was linearly additive for mixtures. The greater increase in the original epsilon-values of the weak absorbers upon complexation with iodine relative to the corresponding increase in the epsilon-values of the strong absorbers led to good recoveries even at the low dose ratios of the weakly absorbing, and often more potent, alkaloids.

Alkaloids↗
PubMed2005

Centrally active nonhormonal hot flash therapies.

Given the problems associated with hormonal therapy, and the prominent problem of hot flashes in menopausal women, there is a need for nonhormonal agents to alleviate hot flashes. Several compounds that appear to act on the central nervous system have been investigated. Potential mechanisms for their effects on hot flashes have been described. Bellergal (no longer available on the US market, where it was known as Bellergal-S), a combination preparation sedative that consists of low-dose phenobarbital, ergotamine tartrate, and levorotatory alkaloids of belladonna, is an old agent that was popular approximately 20 years ago; however, there is limited suggestion of efficacy for this agent. Clonidine, an older antihypertensive drug, is another centrally active agent that has been studied. Randomized trials have demonstrated that it clearly works for reducing hot flashes, but the magnitude of efficacy is somewhat limited. Toxicity from this agent limits its utility in the clinic. Methyldopa is another centrally active agent that has been studied but to a more limited degree. It appears to have minimal efficacy and too much toxicity to make it clinically useful. Anecdotal observations from a number of sources suggested that newer antidepressants can alleviate hot flashes. This led to pilot trials of venlafaxine and paroxetine, with results suggesting benefit from both drugs. Subsequently, randomized, placebo-controlled, double-blind clinical trials of venlafaxine, paroxetine, and fluoxetine were conducted. All 3 of these clinical trials demonstrated statistically significant reductions in hot flashes with these newer antidepressants compared with placebo. Pilot trials of citalopram and mirtazapine, 2 other newer antidepressants, have also suggested efficacy. Toxicity evaluations have suggested that these agents are, again, well tolerated by the majority of patients. A recent trial, however, was unable to demonstrate any benefit for fluoxetine or citalopram over a placebo. Anecdotal observations also suggested that gabapentin was helpful for alleviating hot flashes. This led to pilot trials that again suggested efficacy. Subsequently, 2 large placebo-controlled, randomized, double-blind clinical trials were conducted. Both of these demonstrated statistically significant efficacy for gabapentin compared with a placebo. This drug is relatively well tolerated by most patients. Thus, centrally active nonhormonal agents clearly do decrease hot flashes in women. The most efficacious and clinically appropriate agents for use are newer antidepressants and gabapentin. Continued evaluation of the efficacy and toxicity of these agents is ongoing.

Amines↗
PubMed1980

The chemotherapy of onchocerciasis IV. Further trials with metrifonate.

Thirty-four healthy adult males, moderately to heavily infected with Onchocerca volvulus, were treated daily with metrifonate at 10 mg/kg body weight for either three or six days. The patients' reactions and the effects on the microfilariae were measured on a 'single-blind' basis. Muscarinic effects of acetylcholine were prominent despite the use of belladonna alkaloids, and nicotinic effects--leading to a proximal muscle weakness--occurred in one patient after the fifth dose. A syndrome of polyarthritis, fever and elevated erythrocyte sedimentation rate occurred in 11 patients, in two of whom microfilariae were demonstrated in the joint fluid. The six-day regime destroyed 83% of the microfilarial load and the three-day regime destroyed 72%, but the difference was not statistically significant (as assessed one week after the completion of treatment). It seems unlikely that metrifonate will replace DEC as the 'reference' microfilaricide and attempts to improve its efficacy by employing higher dosage must employ an intermittent dose regime.

Acetylcholine↗
PubMed2005

Potentially inappropriate medication use by elderly persons in U.S. Health Maintenance Organizations, 2000-2001.

OBJECTIVES: To determine rates of potentially inappropriate medication use in elderly persons in managed care plans in the United States in 2000-2001. DESIGN: Cross-sectional study using automated medication-dispensing data. SETTING: Ten geographically distributed health maintenance organizations (HMOs). PARTICIPANTS: One hundred fifty-seven thousand five hundred seventeen members aged 65 years and older enrolled in one of the HMOs. MEASUREMENTS: Prevalence of use of 33 potentially inappropriate medications from January 1, 2000 through June 30, 2001. RESULTS: In 2000-2001, 28.8% (95% confidence interval=28.6-29.1) of elderly individuals received at least one of 33 potentially inappropriate medications. This rate ranged from 23.0% to 36.5% across the 10 HMOs. Approximately 5% of elderly patients received at least one of the 11 medications classified by an expert panel as "always avoid," 13% received at least one of the eight medications that would rarely be considered appropriate, and 17% received at least one of the 14 medications that have some indications but are often misused. Overall, rates of use of these medications were greater in women (32.4%) than in men (24.2%). At least 1% of elderly members received belladonna alkaloids (2.3%), dicyclomine (1.1%), or hyoscyamine (1.2%), each of which multiple expert panels have classified as always inappropriate in patients aged 65 years and older. Seven percent of elderly members received propoxyphene, an analgesic medication considered rarely appropriate in the elderly and a drug that has a long history of limited efficacy and potential for toxicity. CONCLUSION: Recent rates of potentially inappropriate medication use by elderly HMO members were at least as great as in a 1996 national sample. This study highlights the need to understand more fully the rationale behind the continued use of these medications.

Age Distribution↗
PubMed1981

Studies of metrifonate in onchocerciasis.

Metrifonate has been studied in the treatment of infections with Onchocerca volvulus in West Africa. In doses of 10 mg/kg daily for six days, metrifonate was effective against the microfilariae but produced unpleasant reactions due both to the death of the microfilariae and to the muscarinic effects of the drug. In a comparison of 10 mg/kg metrifonate, for 3 doses at 10 day intervals, with diethylcarbamazine (D.E.C.) in a total dose of 6.6 g, metrifonate was significantly less effective than D.E.C. in killing microfilariae but produced significantly fewer adverse effects. In a final study comparing metrifonate 10 mg/kg/day given for 3 or for 6 days there was little difference in their therapeutic effect. However, metrifonate 10 mg/kg given for 6 days produced more severe adverse reactions due largely to the muscarinic and nicotinic effects of acetylcholine and these effects were not prevented by the administration of belladonna alkaloids. Metrifonate 10 mg/kg given for 3 doses at 10 day intervals is effective in the treatment of onchocerciasis but is unlikely to replace diethylcarbamazine. Metrifonate has no action on the adult worms.

Acetylcholine↗
PubMed2005

Asthma: one hundred years of treatment and onward.

There have been four types of drug treatment of asthma that have been used over the past 100 years. Belladonna alkaloids, derived from the thorn-apple plant were used in 1905, and chemically synthesized entities in this class are still in use today. Western medicine began to use adrenergic stimulants approximately 100 years ago, but they were likely used in Asian medicine long before that. Systemic treatment with corticosteroids was introduced into the treatment of asthma in the mid-20th century; inhaled corticosteroids have been in use for over 35 years. The last 40 years have also seen the development of the first targeted asthma treatments: cromones, antileukotrienes, and anti-IgE. As we learn more of the biology of asthma, we anticipate that more effective targeted asthma treatments will be developed.

Administration, Inhalation↗
PubMedDate not supplied

Determination of ergotamine tartrate in tablets by liquid chromatography with fluorescence detection.

A method is presented for the liquid chromatographic (LC) determination of ergotamine tartrate in tablets that is applicable even in the presence of other ingredients such as phenobarbital, belladonna alkaloids, and caffeine. The sample is transferred to a volumetric flask, a small volume of formic acid is added to dissolve and stabilize the ergotamine, and the solution is diluted to volume with methanol. The solution is mixed and filtered through paper. The LC system consists of a Rheodyne injector fitted with a 20 microL loop and a C18 reverse phase column; the mobile phase is acetonitrile-water-triethylamine (700 + 300 + 0.5). Ergotamine tartrate is determined fluorometrically at an excitation wavelength of 250 nm and an emission wavelength of 430 nm. Recovery studies were conducted at the 0.3 and 1.0 mg levels. Average recoveries were 99.6 and 100.8%, respectively; relative standard deviations (RSDs) were 1.08 and 2.21%, respectively. Some commercial preparations containing ergotamine tartrate in combination with other ingredients were also analyzed. The RSDs for 5 determinations of each of 2 ground composites were 0.09 and 0.34%.

Chromatography, Liquid↗
PubMed1979

Reversible toxic psychosis.

Psychotropic medications may produce a toxic confusional state, especially in elderly patients. Tricylcic antidepressants particularly, and the phenothiazines to a lesser extent, may induce these behavioral changes by their anticholinergic activity. The situation may be compounded by the use of more than one psychotropic drug or the addition of an antihistamine or a belladonna alkaloid. Physostigmine can reverse the anticholinergic effects and clear the mental state.

Aged↗
PubMed1994

Evaluation and management of sialorrhea of pregnancy with concomitant hyperemesis.

This article describes two gravid patients who presented with first-trimester sialorrhea and hyperemesis. Although excessive salivation, especially when accompanied by protracted nausea and vomiting, is an unusual occurrence, it can have serious consequences for both the mother and fetus when left untreated. Initially, phenothiazine was prescribed and later belladonna alkaloid was added separately to the two treatment regimens. In order to successfully treat the excessive salivation, it was necessary to control the nausea and vomiting. Eradication of sialorrhea and hyperemesis were effected 10 days posttreatment. For both patients, pregnancy, delivery, and postpartum intervals proceeded uneventfully. Mothers and infants remain in good health 2 years posttreatment.

Adult↗
PubMed1976

Comparative study of the effect of atropine, P2AM, and Buscopan. Total belladonna and hyoscyamus alkaloids on parathion poisoning.

Among the available antidotes used against parathion poisoning, atropine and Buscopan are tolerated in relatively high doses by rats. Hyoscine (in very small doses), T. Bel. Alk. and T. Hyosc. Alk. (better results in small doses, also for dogs), P2AM (of superior antimuscarine action) are redommended with each of the preceding drugs than either alone or in combination with Buscopan.

Animals↗