Catecholamine stimulation, blocking

Certain stimulant actions of catecholamines on various smooth muscles are blocked by alpha blockers such as uterine contraction of certain species, contraction of vas deferens and retractor penis, stimulation of seminal vesicles and vas deferens. Alpha blockers can inhibit ejaculation and produce impotence. Salivary secretion and sweat formation induced by catecholamines is blocked by alpha blockers. 

A piperidine derivative, methylphenidate facilitates the release of catecholamines and blocks their reuptake and degradation (27). It is considered to be a mild central nervous system (CNS) stimulant, which appears to stimulate brain structures in a manner similar to amphetamines (26). A strongly favored treatment for ADHD, methylphenidate prescriptions account for over 90% of prescription stimulants used in the United States (28). Both children and adults who have been diagnosed with ADHD have been treated with methylphenidate with a high degree of success (29,30). A review of the studies in which stimulants were used by children with ADHD indicated significant evidence for improvement in hyperactivity, inattention, and impulsivity (28). 

Other recent reports which indirectly tend to weaken the concept that norepinephrine is the sole alerting neurohumor indicate that (1) imipramine hyperactivity may result from blocking uptake and reducing nervous impulse flow in central serotonin neurons (2) drugs which Inhibit uptake of catecholamines also block serotonin accumulation in rabbit brain stem preparations (3) the increase in overt stimulation caused by 5-hydroxy-tryptophan may be associated with Impaired norepinephrine synthesis rather than increased norepinephrine release and (4) norepinephrine and dopamine inhibit electrical activity of central neurons as determined microelectro-phoretically although another study indicated that norepinephrine does cause neuronal excitation ... 

Methylphenidate like cocaine largely acts by blocking reuptake of monoamines into the presynaptic terminal. Methylphenidate administration produces an increase in the steady-state (tonic) levels of monoamines within the synaptic cleft. Thus, DAT inhibitors, such as methylphenidate, increase extracellular levels of monoamines. In contrast, they decrease the concentrations of the monoamine metabolites that depend upon monoamine oxidase (MAO), that is, HVA, but not catecholamine-o-methyltransferase (COMT), because reuptake by the transporter is required for the formation of these metabolites. By stimulating presynaptic autoreceptors, methylphenidate induced increase in dopamine transmission can also reduce monoamine synthesis, inhibit monoamine neuron firing and reduce subsequent phasic dopamine release. 

Propranolol is a prototype of this series of drugs and is the oldest and most widely used nonselective )3-adrenoblocker. It possesses antianginal, hypotensive, and antiarrhythmic action. Propranolol is a cardiac depressant that acts on the mechanic and electrophysio-logical properties of the myocardium. It can block atrioventricular conductivity and potential automatism of sinus nodes as well as adrenergic stimulation caused by catecholamines nevertheless, it lowers myocardial contractility, heart rate, blood pressure, and the myocardial requirement of oxygen. 

SA node and A-V fibers become dominant. Activation of M2 receptors increases the potassium permeability and reduces cAMP levels, slowing the rate of depolarization and decreasing the excitability of SA node and A-V fiber cells. This results in marked bradycardia and a slowing of A-V conduction that can override the stimulation of the heart by catecholamines released during sympathetic stimulation. In fact, very high doses of a muscarinic agonist can produce lethal bradycardia and A-V block. Choline esters have relatively minor direct effects on ventricular function, but they can produce negative inotropy of the atria. 

Despite the documented efficacy and safety of the psychostimulants, their mechanism of action is not fully understood. Stimulants affect central nervous system (CNS) dopamine (DA) and norepinephrine (NE) pathways crucial in frontal lobe function. The stimulants act by causing release of catecholamines from the DA axons and blocking their reuptake. Methylphenidate releases catecholamines from long-term stores, so its effects can be blocked by pretreatment with reserpine. Amphetamines, on the other hand, release catecholamines from recently formed storage granules near the surface of the presynaptic neuron, so their action is not blocked by reserpine. In addition, the stimulants bind to the DA transporter in striatum (see Figures 2.6 and 2.7) and block the reuptake of both DA and NE. This action reduces the rate that catecholamines are removed from the synapse back into the axon and leads... 

The mechanisms by which 2-PAM exerts its cardiac effects have been studied in experimental animals. At least three classes of action have been attributed to the effects of altered calcium metabolism on autonomic ganglia. A sympathomimetic action of 2-PAM was postulated to explain the increase in blood pressure and the augmented myocardial contractility by one or more of the following mechanisms 2-PAM may not block the release of the endogenous compounds, but may prevent the uptake of catecholamine 1 it may stimulate the release of norepinephrine it Increases myocardial contractility by directly stimulating beta receptors and it increases blood pressure by directly stimulating alpha receptors. 5... 

Taken together with the results obtained by DlPalma s group,117,118 the finding by Barnes et al.H 0f the particularly large effect of prior treatment with reserplne on the response of the arterial pressure to I seems to confirm the Involvement of catecholamine release In this hypertensive response. It Is clear, however, that X also has a direct Inotropic effect on the heart, In that the increase In stroke volume was blocked only partially by any of the three possible antagonists used by Barnes et al. Xn view of the fact that none of the possible antagonists was able to prevent more than about 68.52 of the increase In peripheral resistance Induced by X, this oxime may well have direct stimulant effects on vascular smooth muscle. 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

Monoamines include the catecholamines (dopamine and norepinephrine) and 5-hydroxytryptamine. Although these compounds are present in very small amounts in the CNS, they can be localized using extremely sensitive histochemical methods. These pathways are the site of action of many drugs for example, the CNS stimulants cocaine and amphetamine appear to act primarily at catecholamine synapses. Cocaine blocks the reuptake of dopamine and norepinephrine, whereas amphetamines cause presynaptic terminals to release these transmitters. 

Alpha antagonists are administered primarily to reduce peripheral vascular tone by blocking the alpha-1 receptors located on vascular smooth muscle. When stimulated by endogenous catecholamines (norepinephrine, epinephrine), the alpha-1 receptor initiates vasoconstriction. 

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