Receptors, adrenergic histamine

Monoamine oxidase inhibition Serotonin reuptake inhibition Norepinephrine reuptake inhibition Dopamine reuptake inhibition a2-Adrenergic receptor blockade Serotonin-2A receptor blockade Serotonin-2C receptor blockade Serotonin-3 receptor blockade op-Adrenergic receptor blockade Histamine-1 receptor blockade Muscarinic cholinergic receptor blockade... 

Beyond their action upon SERT and NET, venlafaxine (1), milnacipran (2) and duloxetine (3) are remarkably selective molecules. All three of them have displayed very low in vitro affinity Ki > 3(X)0 nM) for ai- and a2-adrenergic, histamine Hj, muscarinic, and DA D2 receptors, consistent with favorable side-effect profiles. Venlafaxine (1) and duloxetine (3) also have low affinity for a number of serotonergic receptors, and do not inhibit monoamine oxidase A or B. An expanded in vitro receptor profile of >50 receptors and binding sites... 

Risperidone, a novel benzisoxazole derivative, is an atypical antipsychotic medication that combines dopamine D2 receptor antagonism with potent 5-HT2 receptor antagonism. Risperidone has a higher affinity for dopamine D2 receptors than does clozapine. Risperidone also antagonizes dopamine Dj and D4 receptors, aj- and a2-adrenergic receptors, and histamine Hj receptors. Although the optimal dose of risperidone in North American trials was 6 mg/day, subsequent clinical experience has indicated that most patients do well at lower doses of 3-6 mg/day, and elderly patients may require doses as low as 0.5 mg/day. Unlike other atypical antipsychotics. 

The phenothiazines inhibit dopaminergic receptors in the CNS, a property thought to account for their neuroleptic effect. In addition, phenothiazines inhibit muscarinic, a-adrenergic, histaminic, and serotonergic receptors, which accounts for many of their toxic or undesirable side effects. 

Biogenic amine receptors (adrenergic, serotonin, dopamine, muscarinic, histamine)... 

Bupropion (100 mg p.o. b.i.d.) is indicated in the treatment of depression. It is reserved for patients who cannot tolerate or have not responded to other medications. Bupropion does not alter the uptake of serotonin, has an equivocal effect on the uptake of norepinephrine, but blocks the uptake of dopamine. Bupropion has no affinity for alpha-1 and alpha-2-adrenergic receptors, H,-histamine receptors, muscarinic cholinergic receptors, or D2-dopaminergic receptors. It does not cause sedation or orthostatic hypotension. However, because it is structurally related to amphetamine, it may cause insomnia, agitation, and anxiety shortly after initiation of therapy. Bupropion lowers the seizure threshold and hence is contraindicated in patients with a history of seizure disorder (see also Tables 5 through 7). 

Venlafaxine a racemate has no appreciable affinity for muscarinic, alpha-adrenergic, beta-adrenergic, histamine-1, 5-HT-lA, 5-HT-2, dopamine-2, benzodiazepine, or opiate receptors [45] and thus is not expected to induce side-effects caused by interaction of venlafaxine itself with these receptors. However, the possibility remained that metabolites of venlafaxine could have affinity for the above mentioned neuroreceptors and thereby cause unwanted side-effects. 

OH, NHMe. AH three metabolites virtually lacked affinity for dopamine-2, cholinergic, alpha-l-adrenergic, histamine-1 and opiate receptors [47]. The metabolites were also tested for monoamine uptake properties in vitro [47] (Table... 

Minor sites of action cholinergic (muscarinic), alpha-1- and alpha-2-adrenergic, histaminic-1 and dopaminergic receptors CNS and cardiac sodium channels. 

Older tricyclic antidepressants are set in italics. The specificity of action of tricyclic antidepressants (in particular of amitritpyline, imipmmine, doxepine, noitriptyline, maprotiline) is limited because at therapeutic levels ihese drugs also block receptors (H t-histamine, a,-adrenergic, muscarinic). 

Studies have now started to clarify the role of histamine Hi and H2 receptors in the cardiovascular manifestations of anaphylaxis. However, histamine can activate H3 and H4 receptors [56, 57]. Levi and coworkers [58-60] identified H3 receptors as inhibitory heteroreceptors in cardiac adrenergic nerve endings. This suggests a mechanism by which endogenous histamine can activate norepinephrine release in normal and ischemic conditions [61,62]. The functional identification ofH3 receptors in the human heart [59] means that these receptors might be directly and/or indirectly involved in the cardiovascular manifestations of anaphylactic reactions. 

The authors also identified the most common structural motifs unique to ligands of individual classes of GPCRs such as the adrenergic, dopamine, histamine, muscarinic, and serotonin receptors as shown in Table 1. 

Mirtazapine enhances central noradrenergic and serotonergic activity through the antagonism of central presynaptic a2-adrenergic autoreceptors and heteroreceptors. It also antagonizes 5-HT2 and 5-HT3 receptors. It also blocks histamine receptors. 

G-protein coupled receptor family comprises most well-known cell surface receptors including the major drug targets, as previously stated. Early PAL results have been reviewed in several papers, and book chapters. For opiate, NMDA, sigma, benzodiazepine, GABA, acetyl choline, and adrenerg, serotonine receptors see [52,59,60], and for purinerg, histamine, and dopamine receptors see [61]. 

PD Zeprexa is a selective monoaminergic antagonist with high affinity for the following receptors serotonin 5HT, dopamine, muscarinic, histamine, and adrenergic. Its action on schizophrenia is through the antagonism in serotonin and dopamine. 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Finally, a thorough receptor binding study by Raffa and colleagues (1998) showed that hypericin extracts had no effect at adrenergic (alpha or beta), adenosine, angiotensin, benzodiazepine, dopamine, bradykinin, neuropeptide Y, PCP, NMDA, opioid, cholecystokinin A, histamine HI, or nicotinic ACh receptors. Although comprehensive, this study did not look at the binding of any other hypericum constituents. 

Cardiovascular effects Harmala alkaloids have cardiovascular effects (Aarons et al. 1977). Harmine, harmaline, and harmalol decrease heart rate, but increase pulse pressure, peak aortic flow, and myocardial contractile force in dogs. Harmine reduces systemic arterial blood pressure and peripheral vascular resistance. Vascular resistance effects are not mediated by jS-adrenergic or histamine HI receptors. 

P2-adrenergic receptors may function similar to HR2 in humans [196,197]. The role of histamine and other redundant G-protein-coupled receptors in the regulation of inunune/inflammatory pathways in allergic inflammation remain to be intensely focused in future studies. 

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