It will yet be found applicable in the treatment of cerebral engorgements of a chronic character buy evista 60 mg with mastercard womens health zone natural remedies health, and in the treatment of hyperaemia of those organs buy evista 60 mg on-line women's health clinic utah, in the cases in which ergot is used discount evista 60mg with visa women's health gynecological problems. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 255 It is valuable in from one-fourth to one-half teaspoonful doses of the fluid Hydrastis, or colorless Hydrastis, in water, in prostrating night sweats. In its power over the nutrition of muscular structure, it is a most important remedy in many disorders of the womb. It produces contraction of the unstriped muscular fibers, slowly but permanently stimulating the removal of excess of growth. In parturition it is not so immediate or forceful as ergot, but acts mildly in the same manner. In uterine subinvolution, in menorrhagia or metrorrhagia from this cause, it is the best remedy we have. It is useful also in post-partum hemorrhage, but is rather slow in its action when immediate results are demanded. In the incipient stage of the development of tumors within the uterine structure, or fibroid growths, it is not excelled by ergotine. It may be used hypodermically in these cases, and its results are comparatively permanent. He uses the mother tincture in conjunction with conium, giving five drops at a dose three or four times a day, the hydrastis before, the conium after meals. He says: “Sometimes, I mix them and give ten drops of the mixture three times a day. Where the swelling is soft or undulated and painful on pressure, and pain extending into the axilla, we find phytolacca in the same doses better than either. Sometimes, all three remedies are good together, and none of them is valuable in the open cancer. The remedies must be continued a long time to make a decided impression, and their effect is even increased by the same remedies being applied externally in the form of a plaster. In all catarrhal conditions, especially if there be muscular relaxation and general enfeeblement, it is a useful remedy. It is used locally in solution and is of much value as an application wash, irrigating fluid or gargle in all such catarrhal, ulcerating, aphthous, indolent and otherwise unhealthy conditions of mucous surfaces. It is a most useful gargle in aphthous or ulcerated sore mouth, in conditions where the gums are spongy or loosened from the teeth or bleed easily. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 256 Ten minims of a fluid preparation, to the ounce, may be used, or a solution of the hydrochlorate of hydrastine in nasal catarrh, in inflammation of the eyes and in gonorrhea One grain of the hydrochlorate in an ounce of rose water, with or without five grains of the sulphate of zinc, is of superior value in purulent conjunctivitis. The same preparation, diluted, is useful in gonorrhea Five drops of the solution in a dram of warm water is the proper strength. The colorless hydrastis in a solution with a small quantity of the potassium chlorate is sometimes superior in nasal catarrh. It is the best of washes in leucorrhea, whatever the cause, and it can be used freely without danger and in various strengths—from one dram to three, to the pint of hot water. It is of much service when the discharge is thick, yellow, and the membranes relaxed and feeble. It forms an excellent wash in eczema of the anus, with ulcers or fissures within the rectum. Its use may be followed with the application of a zinc ointment, with twenty-five per cent its weight of bismuth subnitrate. In mild solutions of the hydrochlorate of the alkaloid one-fourth grain to the ounce, it is serviceable in catarrh of the bladder, as an irrigating fluid. We find in addition to the tonic influence of this remedy, that it has been used in a number of cases of gall stone, with curative results. Professor Farnum claims to have cured a number of cases with the powdered hydrastis. The cases which he regards amenable to this treatment are, first, ordinary cases of cholelithiasis, where the symptoms are transient and not severe; second, acute inflammatory cases, usually attended with fever, and catarrhal conditions of the gall ducts; third, cases ordinarily called biliary colic. Those, of course, where organic change has not taken place, or where the stones are not impacted, in the gall bladder or in the ducts. He uses it as an efficient remedy in catarrhal jaundice where there is no pain to indicate the presence of gall stones in the ducts. This is in harmony with its influence on general catarrhal conditions of the gastro-intestinal tract. Goss claimed that it had direct catalytic power, and aided the digestion, while it corrected the biliary function. It restores the mucous lining of the gall duct, in the same manner that it influences other mucous surfaces. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 257 Cuthberton gave hydrastis canadensis as a tonic to a pregnant woman who had a goitre of recent appearance. As a result of this observation, he treated twenty-five other cases of goitre at the time of puberty, or during the pregnant state. At times when interference with the function of the reproductive organs seemed to produce reflex irritation. One of the patients had become steadily worse under the use of iodine, the iodides, and thyroid extract. This patient began to improve as soon as hydrastis was given, and was promptly cured with this remedy alone. It has been reported as a remedy for mammary cancer, but its more satisfactory influence is upon painful fulness of the mammary gland, during the menstrual period, or for the treatment of local enlargements occurring more or less suddenly, of a benign character, either in maiden ladies or at the menopause. There is an abundance of authority for the use of hydrastis in conjunction with conium maculatum, in the treatment of non-malignant mammary tumors. Two minims each of these two remedies, in the specific form, was given by Webster before meals and at bed time, in these cases, with satisfactory results. The doctor reports in detail quite a number of cases which were relieved or cured by this treatment. The above named agent is a native of Ceylon where it is used as a remedy for all dropsical conditions. It is but little known in America, but may be received on the reliable authority of the native physicians of Ceylon, who use an infusion of the plant, two ounces to the pint, the entire quantity to be given within twenty-four hours. The remedy produces active diuresis, but the reports are as yet so meager that we have no way of knowing in what way the agent acts upon the organs to produce its desired effects. Physiological Action—Henbane is a narcotic and causes deranged vision, headache, giddiness, dilated pupils, dry throat, hoarseness, weakness of the lower limbs, spasms, cramps, paralysis, loss of speech, or loquacious delirium with hallucinations, followed by a dreamy sleep, according to the amount taken. A continuous use of the medicine causes an eruption of the skin of a red color, which is dry and itching. While power to temporarily increase nerve force—mild stimulant properties—is ascribed to hyoscyamus, that influence is much less marked than belladonna and stramonium, although its general effects are in many ways similar to these agents in medicinal doses.
If these symptoms are due to chemical toxicity purchase evista 60 mg line menstruation issues, the most likely cause is exposure to A buy 60mg evista with amex menstruation 2 fois par mois. The activation of muscarinic receptors in bronchiolar smooth muscle is associated with A order cheap evista on line women's health a-z. Overuse of certain decongestants that are indirect-acting sympathomimetics can lead to a diminished response. With this principle in mind, one can anticipate that hexa- methonium will cause A. The presumptive diagnosis was drug toxicity due to the ingestion of a compound similar to A. Reflex tachycardia is most likely to occur after the systemic administration of A. Which one of the following sites is characterized by adrenergic neurohumoral transmis- sion? Activation of prejunctional 0:2 receptors on sympathetic nerve endings is associated with A. The data in the table below show the effects of four drugs (#1-4) on mean blood pressure administered as individual agents before and after treatment with prazosin. Ocular effects that include mydriasis and fixed far vision are characteristic of A. Following a myocardial infarct, a 40-year-old male patient is being treated prophylacti- cally with propranolol. In terms of adverse effects of the drug, which of the following is most likely to occur with use of this specific beta blocker? A 45-year-old Nobel Prize-winner in chemistry has recently been the recipient of a heart transplant. Patient education has included both verbal and written descriptions of the potential cardiovascular effects of pharmacologic agents. Which one of the following drugs is least likely to cause tachycardia in this patient? Because you know about the problem of distinguishing between cholinergic excess and under- treatment in the myasthenic patient, you would probably recommend that your colleague be given A. A number of pharmacologic treatments can slow the progression of the dis- ease, which can ultimately lead to complete blindness if left untreated. Beta blockers cause ciliary muscle contraction, increasing aqueous humor outflow B. Labetalol is an effective antihypertensive agent that, like propranolol, is capable of block- ing beta receptors. Antagonist Pretreatment Agonist 1 Agonist 2 Agonist 3 J, J, None r Atropine r - r Prazosin i - r J, J, Propranolol - Mecamylamine t - r Identify the agonist drugs from the following list: A. Bradycardia due to vagal stimulation is elicited by activation of muscarinic receptor in the heart. Pilocarpine is present in several mushroom species including Amanita mU5- caria, the ingestion of which is associated with the stimulation of M receptors (parasym- pathomimetic effects). All of the other effects listed are typical of excessive stimulation of M receptors. Urinary retention is a well known adverse effect of drugs that have antagonist effects on muscarinic receptors. In addition to the prototypic drug atropine, M blockers include drugs used in Parkinson disease, such as benztropine. The symptoms of cholinergic excess seen in this child are indicative of exposure to insecticides such as the organophosphate parathion, which cause irreversible inhibition of acetylcholinesterase. Muscarinic receptors present in bronchiolar smooth muscle are of the M 3 subtype coupled via Gq proteins to phospholipase C. Tachyphylaxis, a rapid loss of pharmacologic activity, frequently occurs with indirect-acting sympathomimetics such as amphetamine, ephedrine, and pseudoephedrine. The signs and symptoms experienced by this boy are highly suggestive of the ingestion of a compound with strong muscarinic receptor blocking actions. The leaves and seeds of jimsonweed (Datura stramonium) contain anticholinergic compounds, including atropine, hyoscyamine, and scopolamine-approximately 50 seeds may cause severe toxicity. Although used primarily via inhalation for asthma, systemic effects of albuterol include vasodilation due to its ~2 receptor activation. Methoxamine and phenylephrine are (X- receptor activators causing vasoconstriction, which would result in reflex bradycardia. Ganglion blockers (mecamylamine) prevent autonomic reflexes, and a reflex increase in heart rate could not occur in the presence of a beta blocker (propranolol). A decrease in mean blood pressure, an increase in pulse pressure, plus a marked increase in heart rate are characteristic of a drug such as isoproterenol. A similar mechanism involving Gi protein inhibition of adenylyl cyclaseoccurs with activation of M2 receptors (see answer 6). Of the drugs listed, only isoproterenol causes a decrease in mean blood pres- sure, because it activates beta receptors and has no effect on alpha receptors. Prazosin is an alpha blocker, so one can antici- pate that this drug would antagonize any increases in blood pressure that result from acti- vation of (Xl receptors in the vasculature. Epinephrine (high dose), norepinephrine, and tyramine all exert pressor effects via activation of (Xl receptors. However, only epinephrine is active on ~2 receptors, and this action would be revealed by vasodilation and a reversal of its pressor effects following treatment with an alpha blocker-"epinephrine reversaL" Thus, drug #4 can be identified as epinephrine. Mydriasis and fixed far vision can be due to either muscarinic receptor antagonists or ganglionic blockade. The cholinesterase inhibitor (neostigmine) and alpha blocker (phentolaminelcause miosis. Ocular effects of the beta blocker (timolol) are restricted to decreased formation of aqueous humor by the ciliary epithelium. Mydriasis is associated with blockade of M receptors, and both micturition and sweating result from activation of such receptors. However, reflex bradycardia is not possible following pretreatment with an M blocker. This question is to remind you that indirect-acting sympathomimetics require innervation of the effector organ to exert effects. However, transplanted hearts retain receptors, including those (~l) responsive to direct-acting sympathomimetics. If symptoms improve with a single dose of edrophonium, then an increase in the dose of neostigmine or pyridostigmine is indicated. The effectiveness of labetalol in the management of hypertension and in severe hypertensive states appears to be due to a combination of antagonistic actions at both alpha and beta adrenoceptors. Labetalol is not a ~l selective blocking agent (unlike atenolol and metoprolol), and (unlike pindolol and acebutolol) it lacks intrinsic sympa- thomimetic activity. Labetalol is available for both peroral and parenteral use; unfortu- nately, it blocks ~2 receptors in bronchiolar smooth muscle.
It will also relieve erratic pains of stomach and gastric disorders which depend upon or accompany this condition purchase discount evista line breast cancer 4 cm. If these disorders are present with threatened abortion order 60mg evista overnight delivery women's health clinic jackson wy, the remedy should be combined with viburnum cheap generic evista uk sa health women's health, and both be given in full doses to prevent that condition. It, however, works more perfectly in combination with aletris farinosa and cimicifuga in atonic conditions, while caulophyllum and viburnum act best where irritable conditions are present. In addition, it is a general tonic improving the character of all the organs in their functional operations, and especially improving the tone of the digestive apparatus. It is a liver remedy of rare value, in many cases accomplishing most satisfactory results when there is deficient or perverted action. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 112 Munn of Connecticut used it for many years with very satisfactory results. From another observation its influence would be improved in certain cases by the addition of phytolacca and where there is marked toxemia by echinacea. If the sensation of dragging and weight occurs in the male from cystic disorder, the relief is fully as satisfactory. The general action of the agent in these cases is that of a tonic to the genito-urinary apparatus. It quickly overcomes the phosphatic diathesis, and in urinary irritability is serviceable, especially if from atonic causes. It is useful in impotence, and its properties as an aphrodisiac have been often noted. Physiological Action—Drastic cathartic and violent local irritant, alterative, diuretic, diaphoretic and expectorant. This agent stimulates the chylopoietic system, favorably influencing all of those organs which are supplied by the solar plexus of the great sympathetic. Specific Symptomatology—The conditions to which chelidonium are especially applicable are found in fully developed abdominal plethora, inefficient functional action of the glandular organs of the abdominal cavity, and imperfect, sluggish and deficient circulation of the tissues, glands and organs of this cavity. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 113 This agent operates in harmony with leptandra, podophyllum, iris versicolor, chionanthus and sodium phosphate, in the three following important conditions: Diminished secretion of bile, evidenced by grayish, clay-colored, or very light yellow stools, which will usually float. There may be no evidences of absorption of bile into the blood—no jaundice; or there may be absorption of the bile and jaundice, with its whole train of symptoms, with dark green and fetid stools and dolic; or there may be the above grayish, clay-colored stools and jaundice, with bile in the urine, which is dark yellow or red, very acid, charged with an excess of uric acid crystals. Defective liver circulation is the cause of a long train of remote manifestations, among which are slow pulse, frequent palpitations, a feeling of weight, stiffness and swellings of the hands, feet and limbs, cold extremities, pallid and doughy skin, local and general, edema, dull pain or constant aching in the limbs and muscles, aching in the front head and occiput, vertigo, weariness, irritability, inactivity, irregularity of the bowels-constipation, followed by diarrhea, erratic colicky pains, sallowness, jaundice and other disorders. In disease of the spleen, it relieves congestion and reduces splenic hypertrophy, acting in harmony with chionanthus and grindelia squarrosa. Its action upon the pancreatic glands is satisfactory, relieving congestion and engorgement and irritation, and inducing a better circulation. It will be found an excellent remedy in combination with helonias in the treatment of diabetes mellitus. This agent was used thirty years ago with eminent success in the treatment of biliary calculi. It is now in use for that purpose among many physicians, who consider it superior to any other agent known in preventing their formation. Its influence upon the functional activity of the liver induces a thinner and more profuse secretion of the bile, and it is thus useful in promoting the expulsion of gall stones. It is available also in simple biliousness, hepatic congestion, acute or sub-acute inflammation of the liver, jaundice, due to catarrhal conditions of the ducts, or when dropsy depends upon hepatic trouble. When migraine or supraorbital neuralgia depend upon hepatic difficulties this remedy is indicated. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 114 A patient suffering from a headache which began in the occiput before rising in the morning; poor appetite; cold hands and feet; tongue large, thick, pasty, with a grayish white coat; skin of a dusky hue, was materially benefited by chelidonium, five drops of the fluid extract every two hours. Some of the old writers believe that this agent is superior to arnica or hamamelis, as an external application to bruises and sprains. The specific use externally, is in the application of the juice to warts, corns and epitheliomata, for which it has been widely used, and much evidence accumulated in its favor. In these conditions and in the treatment also of urticaria, eczema and itching eruptions, its careful application, persisted in, cures within a short time. In the treatment of cancer, Denissenko directs that from twenty-two to seventy-five grains of the extract shall be taken internally, dissolved in distilled water or peppermint water, every day throughout the treatment. Into the substance of the tumor, as close as possible to the boundary between it and the healthy tissue, he throws a number of injections of from two to four drops of a mixture of equal weights of the extract, glycerine and distilled water, not exceeding a syringeful in all. If the tumor is ulcerated, he paints its surface twice a day with a mixture of one or two parts of the extract and one part of glycerine. The painting of the ulcerated surfaces gives rise to a light and transitory burning. As a result of the treatment the sallow hue of the skin disappeared and softening of the tumor set in. After from three to five days there formed at the points of injection, fistulous tracts about which the softening process went on with special rapidity. Other investigators have not been as satisfied with its influence in cancers, but it is doubtless of value and deserves further observation. Iron, quinine and other supporting remedies are employed according to the indications. Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 115 The oil of the herb and of the seed is the only preparation of chenopo-dium used. This is strictly an American product, large quantities of the oil being produced in this country though the foreign demand should establish foreign sources of supply. Therapy—This agent has long been used as a remedy for worms but because of an early objection made to its use on the grounds of certain subtle, dangerous properties, it has not come into general use. In sufficient doses of from ten to twenty minims of this oil, it was recommended to expel the round worm. Our own authorities seldom recommended above five minims which was not always sufficient though safer. In the Orient, especially in Singapore and in Sumatra, the oil of chenopodium is extensively employed against hookworm and other intestinal parasites. More than 100,000 cases of hookworm of both the Old and New World types have been treated with practically no untoward effects, and with greater success than with any remedy heretofore employed. In Sumatra, it is used also with equal confidence, in the treatment of roundworm, tapeworm, and whipworm. Weiss of Kisaran treated 5,000 cases of hookworm with hi ghly satisfactory results. There was one case of nephritis which he thought might have followed it, but the case was quickly controlled. Schuffner and Baermann in Sumatra have treated over 40,000 cases without after effects, and with results superior to those obtained from thymol. Administration—The method of the above observers is to give the patient a liquid diet for an evening meal, no breakfast on the following morning. From ten to sixteen minims of the oil is placed on sugar divided into three parts, one part being taken every hour. Two hours after the last dose, a full dose of castor oil and a full dose of chloroform is given.
Your body needs good purchase cheap evista on line menopause memory loss, wholesome food to give it the strength and power it needs to heal buy evista us breast cancer. And just like with emotional changes buy evista 60 mg lowest price breast cancer outfits, you can implement dietary changes at the very beginning of your treatment program and continue choosing more healthful foods as you work on the physical treatments. For more information on how your diet is contributing to your pain, see Chapter 6. Sometimes these sensations are accompanied by radiating pain in the legs and/or feet. All these symptoms can be caused by imbalances within your physical body, mind (e. The following action plan covers two areas: 1) short-term, temporary pain relief and 2) long-term solutions. I always encourage people to work toward the goal of total pain relief—in other words, no more back pain, period. But if you’re too uncomfortable to get through the steps needed for a long-lasting solution, you may want to start with the temporary pain-relief options (listed below). For each category of pain relief (temporary versus long term), I’ve arranged the solutions in order, with the step likely to help you the most listed first. Start with the solution at the top of the list, and then work your way down only if the pain improves but doesn’t completely disappear. Dietary adjustments 171 The 7-Day Back Pain Cure Temporary Pain Relief – Action Plan (see Chapter 9 for details) 1. Muscle-Balance Therapy If you’re suffering from general upper-back or neck pain, 2. Trigger-point therapy you’re probably having a hard time doing daily activities like driving a car, working at the computer, or even brushing your 3. Dietary adjustments muscles “lock up,” making it nearly impossible to move your head or arms. All these symptoms can be caused by problems with your body (usually muscle trauma or imbalances), mind (e. The following action plan covers two areas: 1) short-term, temporary pain relief and 2) long-term solutions. I always encourage people to work toward the goal of total pain relief—in other words, no more back pain, period. But if you’re too uncomfortable to get through the steps needed for the long-lasting solution, you may want to start with the temporary pain-relief options (listed below). For each category of pain relief (temporary versus long term), I’ve arranged the solutions in order, with the step likely to help you the most listed first. Start with the solution at the top of the list, and then work your way down only if the pain improves but doesn’t completely disappear. Dietary adjustments 173 The 7-Day Back Pain Cure Temporary Pain Relief – Action Plan (see Chapter 9 for details) 1. Muscle-Balance Therapy A herniated disc occurs when the outer part of the donut- 2. Trigger-point therapy shaped disc between the vertebrae weakens and the inner part (a gel-like substance) protrudes outward, something like when 3. Emotional troubleshooting any pain until and unless this protrusion touches a nerve. Dietary adjustments Many people live out their lives with one or more herniated discs and never know it. If the protrusion does touch or compress a nerve, it usually causes pain in the lower back, radiating down the back of one or both legs and sometimes causing sharp, needling pain in the bottoms of the feet. If the herniated disc is higher up the spine, radiating pain can occur in the arms. The primary cause of a herniated disc is the excessive compression and torsion that is placed on the spine, which is the result of numerous muscle imbalances throughout the body. In addition, two often overlooked yet major factors are dietary imbalances and negative stress and/or emotions. Herniated disc disease also is referred to as bulging disc, ruptured disc, or degenerative disc disease. The following action plan covers two areas: 1) short-term, temporary pain relief and 2) long-term solutions. I always encourage people to work toward the goal of total pain 175 The 7-Day Back Pain Cure relief—in other words, no more back pain, period. But if you’re too uncomfortable to get through the steps needed for the long-lasting solution, you may want to start with the temporary pain-relief options (listed below). For each category of pain relief (temporary versus long term), I’ve arranged the solutions in order, with the step likely to help you the most listed first. Start with the solution at the top of the list, and then work your way down only if the pain improves but doesn’t completely disappear. With a herniated disc, getting pressure off the spine is critical to recovery, and turning the body upside down is the best way to do that. Reverse gravity opens the spaces between the vertebrae, giving them room to heal and encouraging them to slide back into place. If you have this condition, invest in a quality inversion table immediately (see www. Muscle-Balance Therapy 175 The 7-Day Back Pain Cure Herniated Disc 176 relief—in other words, no more back pain, period. Trigger-point therapy you’re too uncomfortable to get through the steps needed for 4. Emotional troubleshooting the long-lasting solution, you may want to start with the temporary pain-relief options (listed below). Dietary adjustments For each category of pain relief (temporary versus long term), I’ve arranged the solutions in order, with the step likely to help you the most listed first. Start with the solution at the top of the list, and then work your way down only if the pain improves but doesn’t completely disappear. With a herniated disc, getting pressure off the spine is critical to recovery, and turning the body upside down is the best way to do that. Reverse gravity opens the spaces between the vertebrae, giving them room to heal and encouraging them to slide back into place. If you have this condition, invest in a quality inversion table immediately (see www. Most back-pain sufferers and even many medical doctors incorrectly consider sciatica a medical condition. In reality, sciatica isn’t a condition itself but rather a symptom of another underlying condition—like a herniated disc, piriformis syndrome, spinal stenosis, or another back problem. Most of the underlying causes of sciatica mentioned above are caused by muscle imbalances that have been getting worse over time. The following action plan covers two areas: 1) short-term, temporary pain relief and 2) long-term solutions.
The ensuing increase in monoamine transmission order evista american express menstruation underpants, despite the depletion of the vesicular pool 60 mg evista fast delivery women's health clinic buffalo ny, presumably accounts for the effects of iproniazid on the behaviour of reserpine-pretreated rats buy evista canada menopause herbal remedies. In 1958, another agent, imipramine, was discovered by chance to have beneficial effects in depression. Drawing all this evidence together, Schildkraut (1965) concluded that depression was caused by a functional deficit of noradrenergic transmission in the brain. He also thought that the rebound depression and fatigue, which are experienced after the arousing effects of amphetamine have worn off, were due to depletion of neuronal stores of noradrenaline. To this day, there is controversy over whether or not amphetamine has a beneficial effect in depression. Another proposed that a deficit in both noradrenergic and serotonergic transmission is to blame (Maas 1975). Others have argued that an imbalance in the functional output of these two systems is the key factor (Ricci and Wellman 1990). However, they all share a common theme: that disruption of some aspect of monoaminergic transmission in the brain is a causal factor in depression. It is remarkable that, although this theory is often challenged, it has not yet been replaced by a validated alternative and, to this day, central noradrenergic and/or serotonergic systems are primary targets for all established antidepressant drugs. One is to lookfor the neurobiological basis of depression in human subjects and animal models of this condition. The second is to investigate the pharmacology of established antidepressant agents to see whether they consistently augment some, and ideally the same, neurobiological targets in the brain. For obvious reasons, the majority has looked for changes that might affect monoamine function and so the following sections concentrate on these neurotransmitters. For instance, it is not at all certain that neurochemical changes in the plasma or urine give any reliable indication of what is happening in the brain. Measurements in post-mortem brain tissue do not have this problem but the unavoidable delay in collecting tissue samples intro- duces another. Confirmation of the diagnostic status of the subjects is often difficult (especially retrospectively) and any drug treatments they had taken could distort the results. So far, evidence for abnormal peripheral (Elliott 1992) or central (Horton 1992) monoamine function in depression is equivocal, and no consistent biochemical markers have emerged to provide a firm linkbetween the two (Table 20. However, this abnormality is now believed to be associated with a deficit in control of behavioural impulsivity, rather than depression. Evidence for a linkbetween monoaminergic transmission and the therapeutic effects of antidepressant agents is more convincing. Depletion of noradrenaline stores (achieved by administration of the noradrenaline synthesis inhibitor, a-methyl-p-tyrosine) causes a resurgence of depression in patients who are in remission following treatment with antidepressants that selectively target noradrenergic neurons. However, patients who respond to antidepressants that act primarily on serotonergic neurons are unaffected (Delgado et al. It seems that the therapeutic effects of different anti- depressants could well rest on augmenting particular components of central monoamine transmission, whether or not depression itself is explained by a deficit in the functional output of these neurons. One is to provide a behavioural model that can be used to screen potential antidepressant treatments. For this, the behaviour does not have to be an animal analogue of depression: all that is needed is for it to be consistently prevented by established antidepressant agents (i. A second objective is to produce behavioural changes in animals that are analogous to depression so that the model can be used to discover its neurobiological cause(s). This is a far more demanding problem and its success rests on satisfying at least three criteria (see Willner 1984): face validity (i. Procedures that have been suggested as models of depression and used to lookfor neurochemical changes that parallel the onset of the behavioural change, as well as to test how antidepressants affect the behaviour, are listed in Table 20. Those that have been used most, either as a drug screen or in research into the neurobiology of depression, are as follows. These changes echo many of the problems experienced by depressives (disruption of appetite and sleep patterns and cognitive deficits). Also, as in many depressed patients, the concentration of plasma corticosteroids is increased in rats after olfactory bulbectomy (see later). This pattern of changes suggests that bulbectomy disrupts links between limbic areas of the brain and the hypothalamus. Its validity as a model of depression is supported by findings that all physiological and behavioural changes resulting from bulbectomy, that have been reported so far, are normalised by antidepressants from different generic groups. Subsequent work has concentrated on rats and mice, which show a similar behavioural response. Whether or not learned helplessness really is an analogue of depression remains controversial (Maier 1993). Nevertheless, escape deficits in rats are prevented by pretreatment with antidepressants from different generic groups. One of the earliest and most consistent findings with this model was a marked depletion of noradrenaline stores in certain brain regions, particularly the cortex, hippocampus and hypothalamus, of mice that have been exposed to inescapable shock. One school of thought proposes that exhaustion of releasable noradrena- line in the neurons projecting to these brain regions underlies learned helplessness (Anisman and Zacharko 1991). Others highlight the depletion of noradrenaline stores in the locus coeruleus and suggest that a reduction in the release of noradrenaline in this nucleus diminishes the a2-autoreceptor-mediated feedbackinhibition of neuronal firing and that the resulting neuronal hyperactivity explains learned helplessness (Weiss et al. These two theories obviously differ in respect of whether it is an increase or a decrease in noradrenergic transmission in the terminal field that could account for depression. One problem with both these theories is that disruption of noradrenergic trans- mission by selective adrenoceptor antagonists has little impact on the development of escape deficits. However, such antagonists do prevent the reversal of learned helpless- ness by antidepressants (reviewed by Stanford 1995). Also, it would be most unlikely that a deficit in only one neurotransmitter system fully accounts for learned helpless- ness. In short, the widespread neurochemical disruption during learned helplessness suggests that antidepressant drugs could prevent this syndrome by targeting any of several different neurotransmitter systems. Many antidepressants delay the onset and duration of immobility and this action has been widely adopted as a preclinical screen for novel compounds (Porsolt et al. Nevertheless, the behavioural deficits all respond, with varying degrees of specificity, to established antidepressants and central monoamines appear to have a crucial role in the therapeutic effects of these drugs. Some drugs even combine reuptake inhibition with actions which increase transmitter release. Whereas the newer antidepressants are a great improvement in terms of safety and tolerability, imipramine still remains the bench- markfor efficacy. Full appraisals of antidepressants that are already in the clinic and those that are currently under development, together with their likely clinical and commercial impact, are to be found in Cheetham and Heal (2000) and Heal and Cheetham (1999). The enlarged vesicular pool will increase exocytotic release of transmitter, while an increase in cytoplasmic monoamines will both reduce carrier-mediated removal of transmitter from the synapse (because the favourable concentration gradient is reduced) and could even lead to net export of transmitter by the membrane transporter. Like amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. As a result, transmitter accumulates in the cytoplasm and is exported into the synapse via the membrane-bound transporter.