L-dopa stimulant

These agents, like L-dopa, stimulate pituitary growth hormone release in normal subjects and—... 

Morelli M, Cozzolino A, Pinna A, Fenu S, Carta A, Di Chiara G (1993a) L-DOPA stimulates c-fos expression in dopamine denervated striatum by combined activation of Dl and D2 receptors. Brain Res 623 334-336. 

Chihara K, Kashio Y, Kita T, Okimura Y, Kaji H, Abe H, Fujita T (1986) L-DOPA stimulates release of hypothalamic growth hormone-releasing hormone in humans. J Clin Endocrinol Metab (52 466-473. 

The conventional substrates, tyrosine and dopa, can stimulate tyrosinase activity as well as melanization of the cells (766, 206, 248, 249). Positive regulation of tyrosinase by its precursors in vivo that require active protein synthesis was shown for the first time by Slominski et al. (246, 247). Both L-tyrosinase and L-dopa stimulate tyrosinase at the level of translation (248). Depending on dose and time, L-dopa can both stimulate and inhibit tyrosinase mRNA expression (249). Recently, it has been found that tryptophan can stimulate new mRNA-dependent tyrosinase synthesis in B16 murine melanoma cells (38). 

Research for an antidepressant among non-tricyclic compounds with pharmacological effects qualitatively different from those of the conventional tricyclic compounds led to the preparation and testing of a series of indazole derivatives for reserpine-like activity in mice. l-[3-(Dimethylamino)propyl]-5-methyl-3-phenyl-l//-indazole (FS-32 692) antagonizes reserpine-induced effects and potentiates amphetamine-induced self-stimulation and l-Dopa-induced increase in motor activity. FS-32 produces an anticholinergic action mainly on the central nervous System, while the action of imipramine occurs centrally as well as peripherally (79AF511). 

The ability of NB-355 to stimulate locomotor activity and induce dyskinesia in MPTP-treated squirrel monkeys was studied (MPTP induces parkinsonism) [9], NB-355 was similar to L-dopa in stimulating locomotor activity. Furthermore, NB-355 induced less severe dyskinesia than was seen with L-dopa. Some other prodrugs of L-dopa include short-chain alkyl esters (methyl, ethyl, isopropyl, butyl, hydroxypropyl, and hydroxybutyl) intended for rectal absorption [10], These esters of L-dopa have high water solubility (>600 mg/mL). Initial bioavailability studies indicated that all of these esters, with the exception of the hydroxypropyl ester, resulted in significantly greater bioavailability than that obtained with L-dopa itself. However, given the high level of esterase activity in the small intestine, the use of these compounds is limited to rectal administration. 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

Dopamine activity can be enhanced in one of four main ways. Medications can stimulate dopaminergic nerve cells to release dopamine into the synapse. This is the way that stimulants such as methylphenidate (Ritalin), dextroamphetamine (Dexe-drine), and dextroamphetamine/amphetamine (Adderall) work. In addition, certain drugs of abuse, notably cocaine and methamphetamine, act in part in this way. Providing more of the raw material that nerve cells use to manufacture dopamine can also increase dopamine activity. This is the approach that neurologists use when they prescribe L-DOPA (Sinemet) to patients with Parkinson s disease. Nerve cells convert L-DOPA into dopamine. L-DOPA otherwise has little place in the treatment of psychiatric disorders. Dopamine activity can also be increased by medications that directly stimulate dopamine receptors. Bromocriptine, another medication used to... 

Methyldopa (l -pathway directly parallels the synthesis of norepinephrine from dopa illustrated in Figure 6-5. Alpha-methylnorepinephrine is stored in adrenergic nerve vesicles, where it stoichiometrically replaces norepinephrine, and is released by nerve stimulation to interact with postsynaptic adrenoceptors. Flowever, this replacement of norepinephrine by a false transmitter in peripheral neurons is not responsible for methyldopa s antihypertensive effect, because the a-methylnorepinephrine released is an effective agonist at the cx adrenoceptors that mediate peripheral sympathetic constriction of arterioles and venules. In fact, methyldopa s antihypertensive action appears to be due to stimulation of central a adrenoceptors by a-methylnorepinephrine or a-methyldopamine. 

Several lines of evidence show that dopamine (DA) is implicated in the mediation of some obsessive-compulsive behavior. Animal studies demonstrate that high doses of various dopaminergic agents, such as amphetamine, bromocriptine, apomorphine, and L-DOPA, induce stereotyped movements in animals, which resemble compulsive behaviors in OCD patients. Increased dopaminergic neurotransmission may be responsible for this. Human studies consistently report that abuse of stimulants such... 

Levodopa (L-dopa) is a natural intermediate in the biosynthesis of catecholamines in the brain and peripheral adrenergic nerve terminals. In the biologic sequence of events it is converted to dopamine, which in turn serves as a substrate of the neurotransmitter norepinephrine. Levodopa is used successfully in the treatment of Parkinson s syndrome, a disease characterized by dopamine deficiency. When levodopa is administered to an individual with this syndrome, the symptoms of Parkinson s disease are ameliorated, presumably because the drug is converted to dopamine and thereby counteracts the deficiency. Individuals treated with levodopa, especially older men, have been observed to experience a sexual rejuvenation. This effect has led to the belief that levodopa stimulates sexual powers. Consequently, studies with younger men complaining of decreased erectile ability have shown that levodopa increases libido and the incidence of penile erections. Overall, however, these effects are short lived and do not reflect continued satisfactory sexual function and potency. Thus, levodopa is not a true aphrodisiac. The increased sexual activity experienced by parkinsonian patients treated with levodopa may reflect improved well-being and partial recovery of normal sexual functions that were impaired by Parkinson s disease. 

The non-specific tritiation of papaverine ha been described,13 as have methods for the detection of the alkaloid in body fluids.1415 The effects of papaverine on the biochemical fate of thymidine phosphate in the thymus,16 on cyclic AMP and the uptake of calcium in isolated pig auricle,17 on the monosynaptic reflex,18 on the L-DOPA-influenced secretion of GH and PRL,19 on cerebral blood flow,20 and on longitudinal smooth muscle21 have been studied, as have the /3-receptor-stimulant... 

Von Voigtlander, P. E Moore, K. E. 1973, Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum effects of apomorphine, L-DOPA, amanthadine, amphetamine and other psychomotor stimulants, Neuropharmacology, vol. 12, no. 5, pp. 451-462. 

D-TR, 5HT-TR (T D-REL, T 5HT-REL) [ T synaptic D 5HT anti-dyskinetic (i.e. with Parkinson L-DOPA-induced dyskinesis), induces hyperactivity, CNS stimulant, neurotoxic, memory impairment]... 

Figure 2.10 Amphetamine 30, methamphetamine 31, and methylenedioxymethamphetamine 32 (MDMA, ecstasy, XTC) are lipophilic compounds with good oral bioavailability they easily cross the blood-brain barrier to exert central nervous system effects. Dopamine 33, norepinephrine (noradrenalin) 34, and epinephrine (adrenaline) 35 are polar phenethylamines they have poor oral efficacy and do not pass the blood-brain barrier, producing only peripheral effects after intravenous application. Ephedrine 36 has intermediate lipophilicity besides its peripheral effects it also acts as a central stimulant. Although L-dopa 37 is even more polar than dopamine 33, it is orally active and crosses the blood-brain barrier by active transport mediated by the amino acid transporter.

---