Sympathomimetic substances

Note The last two steps give sympathomimetic substances as do all of the steps that follow. If the potency and effects of the DOM analogs are not important to you then you may stop after completing the second step (2,5-dimethoxyamphetamine). 

Sympathomimetic substance with the same effect as noradrenaline. 

Considerable interest has recently been aroused by reports that patients treated with monoamine oxidtise inhibitors may suffer severe hypertensive attacks after taking certain foods, notably cheese - , beans and extracts of yeast . Some of these attacks have proved fatal. The hypertensive crises arise as a result of pressor substances in the offending foods (such as tyramine in cheese) which are absorbed unchanged into the blood stream when intestinal and liver monoamine oxidase is inhibited . Some of the inhibitors (tranylcypromine is an example) also have sympathomimetic actions which will contribute to the hypertensive effect. The administration of sympathomimetic substances—such as adrenaline in a local anaesthetic—to patients treated with monoamine oxidase inhibitor also creates a dangerous situation. The possibility of hypertensive crises clearly constitutes a serious hazard of therapy with these enzyme inhibitors. In many instances their limited effectiveness would not justify the exposure of patients to these hazards. 

Notably, pseudoephedrine is a diastereomer of ephedrine and considerably racemic ephedrine (dl-ephedrine) has not been found naturally, however, it is prepared synthetically and is inactive for commercial purposes. Ephedrine and pseudoephedrine are completely stable compounds under changing temperature conditions, but they are quite unstable when exposed to sunlight or in the presence of oxygen pressure [2]. The unique molecular structure of ephedrine causes its different stereoisomers to be valuable for pharmaceutical applications such as nasal decongestant, pupil dilator, bronchodilator, and central nervous system stimulant. Ephedrine is a sympathomimetic substance and the principle mechanism of ephedrine activity is its influence, by enhancing the activity of noradren-alin, on post-synaptic a- and (3-receptors in the nervous system. Stimulation of a 1-adrenergic receptors produces contraction of vascular smooth muscle. 

As already stated, the number of substances made by chemists for pharmacological examination as possible sympathomimetic amines is enormous and the literature voluminous. Fortunately the latter has been reviewed from time to time, and most recently in the symposium in which Hartung dealt with the correlation of structure and pharmacological action in )3-phenylethylamine derivatives, which includes the more impor-... 

Tests are made by examining the inhibition caused by the substance on the sympathomimetic effects of injected adrenaline and of sympathetic nerve stimulation. Among the recently re-oommended anti-adrenaline drugs are iminazole derivatives (e.g. priscol (VIII))2 and / -haloalkylamines (e.g. dibenamine (IX)). The action of dibenamine is almost certainly that of destroying the receptor patches in the effector organ (p. 37). 

Absence of one or both aromatic hydroxyl groups is associated with an increase in indirect sympathomimetic activity, denoting the ability of a substance to release norepinephrine from its neuronal stores without exerting an agonist action at the adrenoceptor (p. 88). 

Bronchodilators. Narrowing of bronchioles raises airway resistance, e.g in bronchial or bronchitic asthma Several substances that are employed as bronchodilators are described elsewhere in more detail P2-sympathomimetics (p. 84, given by pulmonary, parenteral, or oral route), the methylxanthine theophylline (p. 326, given parenterally or orally), as well as the parasympatholytic ipratropium (pp. 104, 107, given by inhalation). 

If type A inhibitors eventually prove to be as efficacious as other MAOIs and non-MAOIs, there is no doubt that some clinicians will prescribe them with increasing frequency. In addition, if there is minimal risk of adverse interactions with tyramine and other substances (e.g., sympathomimetics), medical and legal concerns about their use will be appreciably reduced. 

Dronabinol (Marinof) [C-ll] [Anriemeric, Appetite Stimulant/ Antivertigo] Uses N/V associated w/ CA chemo appetite stimulation Action Antiemetic 4- V center in the medulla Dose Adults Peds. Antiemetic 5-15 mg/m2/dose q4-6h PRN Adults. Appetite stimulant 2.5 mg PO before lunch dinner max 20 mg/d Caution [C, ] Contra Hx schizophrenia, sesame oil hypersensitivity Disp Caps SE Drowsiness, dizziness, anxiety, mood change, hallucinations, depersonalization, orthostatic 4- BP, tach Interactions T Effects W/ anticholinergics, CNS depressants, EtOH 4- effects of theophylline EMS Use caution w/ sympathomimetics, can T hypertension and tach use caution w/ anticholinergics and antihistamines, can T tach concurrent EtOH use can T CNS depression this is a principal psychoactive substance present in marijuana OD May cause extreme psychiatric effects (anxiety, mood changes and depersonalization) keep pt in a quiet environment and provide reassurance activated charcoal may be effective... 

Subchronic oral administration of lithium causes a time-dependent increase in the substance P level in the striatum, which is prevented by coadministration of haloperidol. In PC 12 pheochromocytoma cells, lithium dramatically increases the intracellular levels of the neuropeptide neurotensin and the mRNA encoding it. An extensive overlap between specific and high-affinity neurotensin binding sites and dopamine perikarya and dendrites has been shown to occur in the mesocorticolimbic and nigrostriatal projection systems. Consistent with this observation are the results of observations showing that cocaine, an indirect sympathomimetic agent that enhances the extrapyramidal dopaminergic activity, increases dramatically the striatal content of neurotensin-like immunoreactivity. 

Amphetamine and methamphetamine possess an essentially pure psychostimulant effect however, substituted derivatives in position 3 and 4 on benzene ring are defined as entactogene [14], This class of substances includes methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), methylenedioxyethyl-amphetamine (MDEA), and others such as the /V-melhyl-l-(3-4-methylenedioxyphenyl)-2-butanamine (MBDB), methoxymethylenedioxyam-phetamine (MMDA) (Fig. 4). All of these substances are more active in the d form. There are also amphetamine-like substances which combine sympathomimetic (euphoric) and hallucinogen effects they are primary amines, trisubstituted on the benzene ring, that produce effects similar to mescaline. Among these the 2,5-dime-thoxy-4-methylamphetamine (DOM) is the most important. 

Cardiovascular system While the hypotensive effect of most anesthetics is sometimes desirable, ischemic injury of tissues could follow reduced perfusion pressure. Should a hypotensive episode during a surgical procedure necessitate treatment, a vasoactive substance must be selected after considering the possibility that the anesthetic present may sensitize the heart to the arrhythmogenic effects of sympathomimetic agents. 

We also looked into the method of action ot mescaline (jf) We found when we searched for phenethylamines that mescaline is always associated with sympathomimetics and other substances which stimulate the sympathetic nervous system such as anorexigenics. 

Indirect sympathomimetics (B) in the narrow sense comprise amphetamine-like substances and cocaine. Cocaine blocks the norepinephrine transporter (NAT), besides acting as a local anesthetic. Amphetamine is taken up into varicosities via NAT, and from there into storage vesicles (via the vesicular monoamine transporter), where it displaces NE into the cytosol. In addition, amphetamine blocks MAO, allowing cytosolic NE concentration to rise unimpeded. This induces the plasmalemmal NAT to transport Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

The adverse effects of amphetamine and related sympathomimetic appetite suppressants are well documented. All of these agents are classified by the U.S. Drug Enforcement Administration (DEA) as controlled substances (classes II-IV) according to their potential for causing addiction (see Table 15.4). Class II agents such as amphetamine are highly abused, with prescription restricted to speeial circumstances class TV anorectic drugs such as sibutramine, phentermine, di-ethylpropion, and mazindol have minimal abuse potential. 

Further studies clarified the operation of mesencephalic enhancer regulation (Knoll and Miklya 1995 Knoll et al. 1996a,b,c). We realized that PEA, the parent compound of (-)-deprenyl, is primarily an endogenous mesencephalic enhancer substance. Since PEA, in higher concentrations, is a highly effective releaser of catecholamines from their intraneuronal stores, this effect covered up completely the enhancer effect of this endogenous amine, which was classified as the prototype of the indirectly acting sympathomimetics. 

Compounds structurally related to the endogenous sympathomimetic amines epinephrine and norepinephrine have classically been employed as appetite suppressants. These agents, of which amphetamine [300-62-9], C9H13N, is the prototypical example, generally retain the phenethylamine, but lack the catechol moiety present in the natural substances. As a consequence, they are well absorbed after oral administration and readily distribute into the central nervous system where they exert their anorectic effects at hypothalamic appetite control centers. A component of their efficacy in promoting weight... 

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