Monoamine A

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

Quaternary amine (or choline ester) Monoamine (a catecholamine) Monamine (a catecholamine) Secondary amine (a catecholamine) Monoamine (an indoleamine) Monoamine (an imidazoleamine)... 

This condition is cansed by a deficiency of one or more of the monoamine nenrotransmitters in the brain (e.g. noradrenaline, dopamine, 5-hydroxytryptamine). One means of increasing the concentration of the neurotransmitters is to inhibit one of the enzymes that degrade the neurotransmitter in the brain. For the monoamines, a key degradative enzyme is monoamine oxidase, which catalyses the reaction... 

Conditions needed to generate a diamino derivative are typically harsher than those required for monoamination. A Japanese patent cites the preparation of 2,6-diamino-4-propylpyridine (115) from 4-propylpyridine (114) with excess sodium amide in Tetralin at 145-195°C (Scheme 45) (80JAP(K)76861). 

As with the other monoamines, a comprehensive study of 5-HT inputs to PC has not been undertaken. Anterograde and retrograde tracing studies have demonstrated a rich... 

The next method Strike has for semi-direct amination is really weird, Strike is really exposing Strike s ignorance of chemistry with this dog. But if one looks hard at the articles cited, the potential is there. The authors came up with this little procedure that produced vicinal diamines out of alkenes [83]. Later they found that if they did a couple of things different, they would end up with a monoamine with the majority product being at the beta carbon. The following is a conjoining of the two paper s experimentals ... 

The addition of N-bromosuccinimide (1.1equiv) to a dichlo-romethane solution containing the alkene (1 equiv) and cyana-mide (4 equiv). The solution was maintained at room temperature (3 days) and then washed with water, dried, and concentrated in vacuo. Treatment of the bromocyanamide [intermediate] with 1% palladium on charcoal in methanol (1h) led to reduction of the for-madine. Addition of base to the reaction mixture (50% aqueous KOH, reflux 6h) followed by extraction with ether gave monoamine. (Yield is 48-64% final amine from alkenes analogous to safrole)... 

Residual monomers in the latex are avoided either by effectively reacting the monomers to polymer or by physical or chemical removal. The use of tert-huty peroxypivalate as a second initiator toward the end of the polymeri2ation or the use of mixed initiator systems of K2S20g and tert-huty peroxyben2oate (56) effectively increases final conversion and decreases residual monomer levels. Spray devolatili2ation of hot latex under reduced pressure has been claimed to be effective (56). Residual acrylonitrile also can be reduced by postreaction with a number of agents such as monoamines (57) and dialkylamines (58), ammonium—alkali metal sulfites (59), unsaturated fatty acids or their glycerides (60,61), their aldehydes, esters of olefinic alcohols, cyanuric acid (62,63), andmyrcene (64). 

The 2-isopropyUiydrazide derivative of 4-CPA is iproclozide [3544-35-2] a pharmaceutical that inhibits monoamine oxidase. 

Metabolism. MetaboHsm of histamine occurs via two principal enzymatic pathways (Fig. 1). Most (50 to 70%) histamine is metabolized to /V-methylhistamine by A/-methyltransferase, and some is metabolized further by monoamine oxidase to /V-methy1imidazo1eacetic acid and excreted in the urine. The remaining 30 to 40% of histamine is metabolized to imidazoleacetic acid by diamine oxidase, also called histaminase. Only 2 to 3% of histamine is excreted unchanged in the urine. 

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

Dopamine. Dopamine (DA) (2) is an intermediate in the synthesis of NE and Epi from tyrosine. DA is localized to the basal ganglia of the brain and is involved in the regulation of motor activity and pituitary hormone release. The actions of DA are terminated by conversion to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase-A and -B (MAO-A and -B) in the neuron following reuptake, or conversion to homovanillic acid (HVA) through the sequential actions of catechol-0-methyl transferase (COMT) and MAO-A and -B in the synaptic cleft. 

Histamine AND histamine antagonists). It is formed from histidine by the enzyme L-histidine decarboxylase. In the periphery, histamine is stored ia mast cells, basophils, cells of the gastric mucosa, and epidermal cells. In the CNS, histamine is released from nerve cells and acts as a neurotransmitter. The actions of histamine ate terrninated by methylation and subsequent oxidation via the enzymes histamine-/V-methyltransferase and monoamine oxidase. 

Octopamine. Octopamiae [104-14-3] (270) is a monoamine found ia the iasect CNS (70). It is involved in feeding behavior... 

Trickle bed reaction of diol (12) using amine solvents (41) has been found effective for producing PDCHA, and heavy hydrocarbon codistiUation may be used to enhance diamine purification from contaminant monoamines (42). Continuous flow amination of the cycloaUphatic diol in a Hquid ammonia mixed feed gives >90% yields of cycloaUphatic diamine over reduced Co /Ni/Cu catalyst on phosphoric acid-treated alumina at 220°C with to yield a system pressure of 30 MPa (4350 psi) (43). 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Reversible Inhibitors of Monoamine Oxidase. Selective MAO-A inhibitors, which aie leveisible (so-called RIMAs), have also been developed, theiefoie substantially leduciag the potential foi food and dmg iateiactions. Indeed, the tyiamine-potentiating effects of these dmgs is much reduced compared with the irreversible MAO inhibitors. The RIMAs represent effective and safer alternatives to the older MAO inhibitors. The only marketed RIMAs ate toloxatone [29218-27-7] and moclobemide (55). The latter is used widely as an effective, weU-tolerated antidepressant. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Mitochondrial monoamine oxidase, 1, 253 Mitomycin synthesis, 7, 658, 659 Mitomycin-A, 7, 93 Mitomycin-B, 7, 93 Mitomycin-C, 7, 93 as antitumor drug, 4, 374 Mixed function oxidases, 1, 224 Mobam... 

Pargyline hydrochloride (Eutonyl, (V-methyl-n-propargylbenzylamine hydrochloride) [306-07-0] M 195.7, m 154-155 , 155 , pK 6.9. Recrystd from EtOH-Et20 and dried in vacuo. It is very soluble in H2O, in which it is unstable. The free base has b 101-103°/ 1mm. It is a glucuronyl transferase inducer and a monoamine oxidase inhibitor, [von Braun et al. Justus Liebigs Ann Chem 445 205 1928, Yeh and Mitchell Experientia 28 298 1972 Langslrom et al. Science 225 1480 1984.]... 

Monoamine oxidase (MAO) inactivates serotonergic and catecholaimnergic neurotransmitters MAO (A and B) inhibitors exhibit mood elevatmg properties 5-Fluoro-Ot-methyltryptamine 19) is an important MAO A-seleUive inhibitor In the treatment of certam depressive illnesses, 4-fluorotranylcypromine (20b) is 10 tunes more potent than the parent tranylcypromme (TCP, 20a) The enhanced m vivo activity may be due to increased lipophihcity at20b and/or to blockade of metabohc para hydroxylation [52]... 

With monoamines, the oxazolones give the normal ring-opened products, A-TFA amino acid amides, but with aniline both forms... 

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