Dual action

Another interesting approach to obtaining potent, broad-spectmm activity has been reported (127). The "dual-action" antibacterial concept involves incorporation of two moieties having complimentary antibacterial modes of action into the same molecule, and uses the mode of action of one part to release the second antibacterial at the site of action. This approach is exemplified in Ro 23—9424 (47) (127), which uses the mode of action and reactivity of the cephalosporin moiety (Fig. 2) to release the quinolone portion. 

Chemically active These filters are similar in design to the non-active depth units but the filtering media used are so chosen that contaminants adhere by chemical attraction. Thus there is a dual action, mechanical and chemical. The materials used include various activated clays. Fuller s earth, charcoal and chemically treated paper. Their cleansing action is much more thorough than that of the purely mechanical devices, for they are capable of removing matter actually in solution in the oil. 

Primatene Dual Action Tablets—theophylline, ephedrine, guaifenesin... 

While most investigations show that sea snake neurotoxins are postsynaptic type, Gawade and Gaitonde (23) stated that Enhydrina schistosa major toxin has dual actions or postsynaptic as well as presynaptic toxicity. E, schistosa venom phospholipase A is both neurotoxic and myotoxic. Neurotoxic action of the enzyme is weak so that there is sufficient time for myonecrotic action to take place (24), Sea snake, L. semifasciata toxin also inhibits transmission in autonomic ganglia, but has no effect on transmission in choroid neurons. 

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

Opioids act in the brain and within the dorsal horn of the spinal cord, where their actions are better understood. The actions of opioids important for analgesia and their side-effects involve pre- and postsynaptic effects (1) reduced transmitter release from nerve terminals so that neurons are less excited by excitatory transmitters, and (2) direct inhibitions of neuronal firing so that the information flow from the neuron is reduced but also inhibitions of inhibitory neurons leading to disinhibition. This dual action of opioids can result in a total block of sensory inputs as they arrive in the spinal cord (Fig. 21.5). Thus any new drug would have to equal this dual action in controlling both transmitter release and neuronal firing. 

A recent patent of invention describes 3,4-bis(furazan-3-yl)furoxan, with general formula 53 and 54 (Fig. 14), able to generate NO and inhibit platelet aggregation [167]. Another invention has claimed Bfx with dual action as platelet aggregation inhibitors and antianginals, being compoimd 55 (Fig. 14) one of the presented example [168]. 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

Pierce PA, Peroutka SJ. (1990b). d-Lysergic acid diethylamide differentially affects the dual actions of 5-hydrox ryptamine on cortical neurons. Neuropharmacology. 29(8) 705-12. 

Nickerson, B., Cunningham, B., and Scypinski, S. (1995). The use of capillary electrophoresis to monitor the stability of a dual-action cephalosporin in solution.. Pharm. Biomed. Anal. 14, 73—83. 

Venlafaxine (Effexor, Effexor XR). Venlafaxine works by blocking the reuptake of both serotonin and norepinephrine. Because of this dual action, some believe that venlafaxine may be more effective than the SSRIs when treating severe depression. Its side effects and toxicity are similar to the SSRIs with abdominal discomfort, sexual dysfunction, and anxiety being commonly reported. At higher doses, it may mildly elevate blood pressure therefore, blood pressure should be checked periodically. When stopping venlafaxine, serotonin discontinuation symptoms may be especially problematic. Therefore, gradually tapering of the dose every 2-4 weeks is recommended. 

Milnacipran is also a dual-action antidepressant which, like venlafaxine, has been shown to be more effective than the SSRIs in the treatment of severe, hospitalized and suicidally depressed patients. At lower therapeutic doses, milnacipran blocks the noradrenaline transporters and therefore resembles the NRI antidepressants. Higher doses result in the serotonergic component becoming apparent (i.e. an SSRI-like action). The main problem with milnacipram appears to be its lack of linear kinetics with some evidence that it has a U-shaped dose-response curve (Figure 7.3). 

Neuroanatomically both the locus coeruleus and the raphe nuclei project to the spinal cord where they gate sensory pathways from the skeletomuscular areas. As there is evidence that both noradrenaline and 5-HT are dysfunctional in depression, it is perhaps not surprising to find that the pain threshold is often reduced in patients with depression. Conversely, different types of antidepressants have been shown to have an antinociceptive effect in both rodent models of neuropathic pain, and clinically in fibromyalgia, chronic fatigue syndrome, postherpetic neuralgia and diabetic neuropathy. In general, it would appear that the dual action antidepressants (such as the TCAs and SNRIs) are more effective than the SSRIs. 

Administer a high therapeutic dose of a "dual action" antidepressant such as venlafaxine or possibly mirtazepine. A discontinuation syndrome may occur if venlafaxine is abruptly withdrawn. The... 

Finally, a few drugs have dual action— both direct and indirect. Dopamine, ephedrine, phenylpropanolamine, metaraminol, and amphetamines all belong to this group. 

Pernar L, Curtis AL, Vale WW, Rivier JE, Valentino RJ (2004) Selective activation of corticotropin-releasing factor-2 receptors on neurochemicaUy identified neurons in the rat dorsal raphe nucleus reveals dual actions. J Neimosci 24 1305-1311 Petty F, Kramer G, Wilson L, Jordan S (1994) In vivo serotonin release and learned helplessness. Psychiatry Res 52 285-293... 

The depressant effects of propranolol on the A-V node are more pronounced than are the direct depressant effects of quinidine. This is due to propranolol s dual actions of p-blockade and direct myocardial depression. Propranolol administration results in a decrease in A-V conduction velocity and an increase in the A-V nodal refractory period. Propranolol does not display the anticholinergic actions of quinidine and other antiarrhythmic agents. 

Opioids depress respiration via the ji2-receptor at the level of the medulla and thereby increase PCO2. Opioids reduce respiration, an effect that is fatal in the case of overdose, by a dual action. The opioids decrease both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Cardiovascular function and the response to hypoxia are not compromised. By contrast, tolerance to the respiratory depressant effects of the opioids does not appear to occur, while tolerance to the emetic effects of the opioids occurs upon repeated administration. The area postrema chemoreceptor trigger zone of the medulla mediates opioid-induced vomiting. 

The dual action of milnacipran would also make it an appropriate candidate for testing whether this type of compound could bring about more rapid onset of response. However, studies requiring more frequent assessments have not yet been carried out. 

It has a dual action. Hyperpolarization effect of piperazine moiety causes paralysis of the worms and alteration in microfilarial surface membrane makes them susceptible to destruction by host defence mechanism. 

Asthma products Bronkaid Dual Action Primatene Mist Primatene Tablets... 

Succinylcholine is a depolarizing blockader. It depolarizes (stimulates) the membrane and then blocks (antagonizes) it. This dual action is not uncommon in drugs. Such activity is termed agonist-antagonist. 

---