Dual-action drug

A dual action drug is a compound which combines two desired different, pharmacological actions at a similarly efficacious dose (IUPAC). 

In addition to a reversal in potency, a dual-action drug may show equipotency for one activity. Carvedilol (Fig. 6) is a nonselective p-adrenoceptor antagonist with vasodilator activity used in the treatment of hypertension and angina. (iS)-Carvedilol is a potent competitive inhibitor at pi-adrenoceptors, whereas the 7 -enantiomer is considerably less potent, with pA2 values of 9.4 and 3.9 for (S)- and (7 )-carvedilol, respectively [39]. In contrast, the enantiomers are essentially equipotent with respect to ai-adrenoceptor blockade, with pA2 values of 7.87 and 7.79 for the S- and / -enantiomers, respectively [39]. Thus the vasodilator and antihypertensive effects of the drug arise as a result of ai-adrenoceptor blockade of both enantiomers and the pi-blockade from the -enantiomer which prevents reflex tachycardia. Similarly to amosulalol, outlined above, the lack of stereoselectivity with respect to ai-adrenoceptor blockade is presumably associated with the hydroxy group being located in a noncritical region of the molecule for receptor interaction. 

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. 

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... 

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

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. 

The mainstay of medication treatment for GAD is, once again, antidepressants. Their success in alleviating or eliminating anxiety is comparable to that of benzodiazepines but with many of the advantages discussed earlier. Both SSRIs and dual-action antidepressants (like venla-faxine and, sometimes, some of the older TCAs) are drugs commonly used. Overall, treatment discontinuation often leads to the relapse of symptoms, although the actual rates are poorly understood at this time. 

Among the treatment options, topical decongestants, topical and oral antihistamines, mast cell stabilizers, dual-action/multiaction drugs, and certain nonsteroidal antiinflammatory agents have proven useful for alleviating the signs and symptoms associated with ocular allergic reactions. Homeopathic preparations have also become of interest to the ophthalmic community, and their scientific... 

Mast cell stabilizers prevent the mast cell from degranulating and therefore the subsequent release of mediators. However, once the mast cells have already degranulated, mast cell stabilizers are ineffective against the released mediators. Combination drugs with both mast cell-stabilizing and antihistamine effects provide both longterm treatment and a more rapid relief of symptoms. Drugs with this dual-action or multiaction mechanism include azelastine, epinastine, ketotifen, and olopatadine (Table 13-7). 

Keywords Dual action Increment of potency Receptor dimerization Twin drug Triplet drug... 

An elegant design of a dual-action prodrug by coupling E09 with another anticancer drug (3, Scheme 2) has been proposed in which the dual-action prodrug, upon reduction, releases two active anticancer drugs.27... 

Felbamate is effective in both the maximal electroshock and pentylenetetrazol seizure models. Clinically relevant concentrations of felbamate inhibit N-methyl-D-aspartate (NMDA)-evoked responses and potentiate gamma-aminobutyric acid (GABA)-evoked responses in wholecell, voltage-clamp recordings of cultured rat hippocampal neurons. This dual action on excitatory and inhibitory transmitter response may contribute to the wide spectrum of action of the drug in seizure models. 

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