Toxicity presynaptic

While most investigations show that sea snake neurotoxins are postsynaptic type, Gawade and Gaitonde (23) stated that Enhydrina schistosa major toxin has dual actions or postsynaptic as well as presynaptic toxicity. E, schistosa venom phospholipase A is both neurotoxic and myotoxic. Neurotoxic action of the enzyme is weak so that there is sufficient time for myonecrotic action to take place (24), Sea snake, L. semifasciata toxin also inhibits transmission in autonomic ganglia, but has no effect on transmission in choroid neurons. 

The TCA drugs have lost their place as first-line therapy for depression because of their bothersome side effects (Table 33.2) at therapeutic doses and lethal effects in toxic doses. In addition to their presynaptic effects on the neuronal uptake of norepinephrine and serotonin, they block several postsynaptic receptors. They are potent cholinergic muscarinic receptor antagonists, resulting in symptoms such as dry mouth, constipation, tachycardia, blurred vision and urinary retention. Blockade of histamine receptors (Hi) often results in sedation and weight gain. Antagonism of aj-adrenoceptors in the vasculature can cause orthostatic hypotension. 

Amphetamine used at high doses can provoke a toxic syndrome ( amphetamine psychosis ) in healthy subjects that shows certain similarities to schizophrenic psychoses. Like cocaine, high-dose amphetamine is known to trigger a massive release of dopamine and noradrenaline from presynaptic sites and thus to produce a temporary excess supply of both neurotransmitters at the respective synapses. 

Gabapentin Decreases excitatory transmission by acting on VG Ca2+ channels presynaptically(a25 subunit) Bioavailability 50%, decreasing with increasing doses not bound to plasma proteins not metabolized ti/2 6—8 h Generalized tonic-clonic seizures, partial seizures, generalized seizures Toxicity Somnolence, dizziness, ataxia Interactions Minimal... 

Tizanidine o -Adrenoceptor agonist in the spinal cord Presynaptic and postsynaptic inhibition of reflex motor output Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis Renal and hepatic elimination t duration, 3-6 h Toxicities Weakness, sedation hypotension... 

Bupropion Increased norepinephrine and dopamine activity Presynaptic release of catecholamines Major depression smoking cessation (bupropion) sedation Extensive metabolism in liver Toxicity Lowers seizure threshold (amoxapine,... 

The most commonly used agents to enhance attention in attention deficit disorder are the stimulants methylphenidate and ( -amphetamine. Other effective stimulants are not as widely used, pemoline because of liver toxicity and methamphetamine because of its greater abuse potential. Methylphenidate and ( -amphetamine act predominantly by releasing dopamine from presynaptic dopamine terminals (Figs. 12— 2 and 12—3). These agents not only block the dopamine transporter but may actually... 

Chang CC, Su MJ (1982) Presynaptic toxicity of the histidine-modified, phospholipase A2-inactive, beta-bungarotoxin, crotoxin and notexin. Toxicon 20 895-905... 

Two drugs widely used to control diarrhea are diphenoxylate [di PHEN ox a late and loperamide [loe PER a mide]. Both are analogues of meperidine (see p. 138) and have opioid-like actions on the gut, activating presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis. Side effects include drowsiness, abdominal cramps and dizziness. Since these drugs can cause toxic megacolon, they should not be used in young children or patients with severe colitis. 

Subsequently, several studies have provided more detailed information on domoic acid action as an excitotoxin. The presynaptic action of domoic acid to induce glutamate release was extended to include other excitatoiy and inhibitoiy neurotransmitters and linked to the entiy of calcium through voltage operated calcium channels, suggesting that domoic acid toxicity may involve multiple transmitters (Brown and Nijjar 1995 Duran et al. 1995a Malva et al. 1996). Domoic acid effects on intracellular calcium were next characterized by FURA-2 imaging of the hilar region of individual... 

Tsai, l.-H., Liu, H.-C., and Chang, T. (1987). Toxicity domain in presynaptically toxic phospholipase A2 of snake venom. Biochim. Biophys. Acta 916,94-99. 

The extreme toxicity of clostridial neurotoxins (CNTs) derives from their absolute neurospecificity as well as from catalytic activity. TeTx and BoNTs bind specifically to the neuromuscular junction (NMJ) of motor neurons. The identity of the receptor(s) on the presynaptic membrane is unknown, but their extreme toxicity suggests that the binding affinity to the cognate receptor must be very high. The receptor-bound toxin is internalized at the presynaptic membrane of the NMJ and gains access to the neuronal cytosol. Here it blocks the release of acetylcholine (ACh), causing a flaccid paralysis (Simpson,... 

Black Widow spider venom contains several different protein fractions. The most significant component of the venom is the neurotoxin, a-latrotoxin. This neurotoxin acts at the presynaptic membrane of the neuronal and the neuromuscular junctions. The binding of the a-latrotoxin results in the opening of nonspecific cation channels, a massive influx of calcium, release of acetylcholine and norepinephrine and decreased uptake of the neurotransmitter. The neurotransmitter release is most likely responsible for hypertension, muscle fasciculations, and spasms frequently experienced by victims of a bite. Later, generalized muscle weakness and labored breathing may develop in severe cases. While the venom of the black widow spider has been characterized as being more potent than that of many poisonous snakes, the small amount of venom injected limits the degree of toxicity. 

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