Peripheral actions

Muscle relaxant. A compound that, by either central or peripheral actions, decreases muscle tension. 

Effect Reduced fat absorption Appetite suppression Appetite suppression, peripheral actions... 

Peripheral mAChRs are known to mediate the well-documented actions of ACh at parasympathetically innervated effector tissues (organs) including heart, endocrine and exocrine glands, and smooth muscle tissues [2, 4]. The most prominent peripheral actions mediated by activation of these receptors are reduced heart rate and cardiac contractility, contraction of... 

It is perhaps easier to identify some of the central functions of DA than that of the other monoamines because not only does it have distinctive central pathways associated with particular brain areas, but it has few peripheral actions. Also the actions of its antagonists reveal its central effects. These are summarised in Table 7.4. 

Vasopressin is closely related to oxytocin and both peptides are cyclic in that they contain a disulphide bridge. Although much is known about the peripheral actions of the peptides the extent of our current knowledge of their possible CNS function is that vasopressin appears to act as a cognitive enhancer and has positive effects on learning processes in animals. Vasopressin acts on three receptors, Via and b and a V2 receptor. 

Bradykinin is another chemical with important peripheral actions but, as yet, cannot be manipulated in any direct way by drugs. It is a product of plasma kininogens that find their way to C-fibre endings following plasma extravasation in response to tissue... 

This peripheral activity may be a rational basis for the use of systemic local anaesthetics in neuropathic states since ectopic activity in damaged nerves has been shown to be highly sensitive to systemic sodium channel blockers. This too is probably part of the basis for the analgesic effects of established effective anti-convulsants that block sodium channels such as carbamazepine, although central actions are important and may even predominate. The precise actions of excitability blockers therefore remains hazy as does any clear basis for the effectiveness of antidepressants and other adrenergic agents in the treatment of neuropathic pain as both central and peripheral actions, including sympathetic effects are possible. 

In summary, primary amine and monoalkyl derivatives of tryptamine have not yet been demonstrated to produce hallucinogenic effects in man or to consistently produce profound behavioral effects in animals. Admittedly, relatively few compounds have been examined, and few studies have been conducted. Nevertheless, present evidence suggests that these derivatives, by virtue of their inability to penetrate the blood-brain barrier and/or their rapid metabolism, may not be able to achieve adequate brain levels to elicit effects. In some cases, these factors may lead to masking of potential central effects by peripheral actions of the compounds or their metabolites. 

Martin and co-workers (142,143) have found that, in animals, tryptamine produced many of the physiologic effects characteristic of LSD however, it does not appear to elicit behavioral effects similar to those of LSD. At relatively high doses, 5-methoxytryptamine (24) does produce some behavioral effects in rats (66,242) and in nonhuman primates (101). Vogel (242) has suggested that the disruptive effects of 5-methoxytryptamine might be due to the peripheral actions of this agent. Tryptamine had no effect on acquisition of avoidance behavior, whereas 5-methoxytryptamine slightly decreased such behavior (240). Both tryptamine and 5-methoxytryptamine produced discriminative effects in rats... 

Anandamide may reduce pain by a peripheral action, by acting on CB 1-like receptors located outside the CNS (Calignano et al. 1998). Palmitylethanolamide (PEA) is an endocannabinoid that is coreleased with anandamide and activates peripheral CB2 receptors. When the two are administered together, they show a 100-fold synergistic effect on analgesic measures. Measurements of anandamide and PEA levels in the skin show that there are sufficient amounts to create tonic activation of local cannabinoid receptors. Thus, endocannabinoids may tonically inhibit cutaneous pain. 

Opioids. Activation of opioid receptors in the enteric nerve plexus results in inhibition of propulsive motor activity and enhancement of segmentation activity. This antidiarrheal effect was formerly induced by application of opium tincture (paregoric) containing morphine. Because of the CNS effects (sedation, respiratory depression, physical dependence), derivatives with peripheral actions have been developed. Whereas diphenoxylate can still produce clear CNS effects, loperamide does not Lullmann, Color Atlas of Pharmacology... 

It is worth mentioning that iV-allylic substitution in a number of morphine derivatives, as a rule, leads to antagonistic properties. Naloxone is a few times stronger than nalorphine as an antagonist. It blocks opiate receptors. It eliminates central and peripheral action of opioids, including respiratory depression. Naloxone is used upon overdose of narcotic analgesics.Synonyms for this drug are narkan, talwin, and others. 

Quinazoline alkaloids are known as biologically active compounds. Arborine inhibits the peripheral action of acetylcholine and induces a fall in blood pressure. Febrifugine is an anti-malarial agent and vasicine acts as a uterine stimulant. Glomerin and homoglomerin are alkaloids of the defensive system in some organisms (e.g., in the glomerid millipede). 

Wang Y, Small DL, Stanimhovic DB, et al (1997) AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. Nature 389 502-504 Warncke T, Jorimi E, Stubhaug A (1997) Local treatment with the N-methyl-n-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action. Neurosci Lett 227 1-4... 

Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stim-ulating effect in addition to its peripheral actions. The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with aU indirectly acting adrenomimetic amines,... 

Mechanism of Action An ergot alkaloid that centrally acts and decreases vascular tone, slows heart rate. Peripheral action blocks alpha-adrenergic receptors. Therapeutic Effect Improved Oj uptake and improves cerebral metabolism. Pharmacohinetics Rapidly, incompletely absorbed from GI tract. Metabolized in liver. Eliminated primarily in feces. Half-life 2-5 hr. 

Mechanism of Action A sympathomimetic amine related to amphetamine and ephe-drine that enhances CNS stimulant activity. Peripheral actions include elevation of... 

Analgesic action Salicylates relieve pain by both central and peripheral action. The site of action of central analgesia seems to be the hypothalamus. It does not have cortical action on the reaction component of the pain but raises the threshold to pain perception. Unlike morphine, they do not produce sedation and there is no drug tolerance or dependence and are not effective against visceral pain. 

Blood pressure Because of vasoconstriction (ttj) and vasodilatation (P ) action of adrenaline, the net result is decrease in total peripheral resistance. Although adrenaline increases the systolic blood pressure but simultaneously lowers the blood pressure by its peripheral action. The rise in systolic blood pressure is often followed by decrease in blood pressure, adrenaline in such doses activates both a and b receptors. But mean blood pressure rises with increase in pulse pressure. 

Domperidone is structurally related to droperidol. It does not cross the blood-brain barrier to the same extent as droperidol so has fewer sedative side effects. It has an effect both on the CTZ and by a peripheral action on the stomach by increasing gastric emptying. Timing of the dose of drug is important for maximal efficacy. 

Reduced motility and secretion can lead to constipation, which is the most common side-effect of chronic opioid treatment (Mancini and Bruera, 1998). Opioid-induced constipation can increase to the stage of megacolon or paralytic ileus. Therefore chronic opioid treatment should be accompanied by concomitant use of laxatives. Besides their peripheral actions, opioids are involved in the central... 

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