Ketamine mechanism

At low doses, ketamine may result in impairment of attention, learning ability, and memory, and at high doses it has been associated with delirium, amnesia, impaired motor function, hypertension, depression, and respiratory depression (Krystal et al. 1994). Another mechanism of action appears to be a blocking of the reuptake of catecholamines. This effect leads to an increase in heart rate and blood pressure (Reich and Silvay 1989). 

The results demonstrate anticonvulsant properties of PCP and ketamine in two quite different seizure models. On the one hand, ketamine was effective in antagonizing several components of PTZ activity. Others have previously reported anti-PTZ effects of ketamine. However, the present results demonstrate that the anticonvulsant effects of ketamine against PTZ seizures closely resembled the effects of phenobarbital in that both compounds delayed clonic convulsions and prevented tonic extension. Moreover, a low dose of ketamine, which alone showed no anticonvulsant effect or overt behavioral changes, potentiated the anti-PTZ effects of phenobarbita 1. These findings suggest that ketamine possesses selective anticonvulsant properties. The anticonvulsant mechanism of action for phenobarbital is not known. However, the similarities between ketamine and phenobarbital, and the interaction between the two compounds, suggest a common mechanism or site of acti on. 

Marwah, J. El ectrophysiological studies of ketamine action in frog skeletal muscle. Neuropharmacoloqy 19 765-772, 1980. Marwah, J. Candidate mechanisms underlying phencyclidine-induced psychosis An electrophysiologica 1, behavioral and biochemical... 

The ion-channel blocking mechanism has been widely tested and found to be important in both pharmacology and physiology. Examples are the block of nerve and cardiac sodium channels by local anesthetics, or block of NMDA receptor channels by Mg2+ and the anesthetic ketamine. The channel-block mechanism was first used quantitatively to describe block of the squid axon K+ current by tetraethylammonium (TEA) ions. The effects of channel blockers on synaptic potentials and synaptic currents were investigated, particularly at the neuromuscular junction, and the development of the single-channel recording technique allowed channel blockages to be observed directly for the first time. 

The mechanisms of action of phencyclidine and ketamine are complex (Gorelick Balster, 1995). The drugs are non-competitive antagonists at NMDA receptors, and also bind to associated phencyclidine/sigma opioid receptors. They also have agonist actions at dopamine receptors, complex interactions with both nicotinic and muscarinic acetylcholine receptors and poorly understood interactions with noradrenergic and serotonergic systems. These multiple actions may combine to produce delirium and psychotic reactions. 

Ketamine and also tiletamine are structurally and pharmacologically related to phencyclidine. Its mechanism of action is not well understood. It has been suggested that it blocks the membrane effects of the excitatory neurotransmitter glutamic acid. Ketamine produces dissociative anesthesia, which means that the patient seems to be awake but there are no responses to sensory stimuli. Ketamine, which can be administered IV or IM, has strong analgesic activity. It is especially indicated for interventions of short duration without any need for skeletal... 

The uncompetitive NMDA receptor antagonist ketamine has been available for clinical use as an anaesthetic for 40 years (Domino et al. 1965). Ketamine is effective in various animal models of hyperalgesia and allodynia and has been reported to have antinociceptive effects in some of these models at doses devoid of obvious side-effects. Others, however, have reported that the effects of ketamine are only seen at doses producing ataxia (see Parsons 2001 for review). Ketamine reportedly inhibits the area of secondary hyperalgesia induced by chemical (Park et al. 1995) or thermal stimuli (Ilkjaer et al. 1996 Warncke et al. 1997) and inhibits temporal siunmation of repeated mechanical (Warncke et al. 1997) and electrical stimuli (Arendtnielsen et al. 1995 Andersen et al. 

Another member of the arylcyclohexylamine structural class is ketamine, which is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, meaning it disables certain higher-function signaling mechanisms in the brain (consciousness, memory, perception, and motor activity) from lower functions (breathing and heart rate). Ketamine is manufactured commercially for use as a surgical anesthetic for both humans and animals. 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Ketamine (Figure 25-2) produces dissociative anesthesia, which is characterized by catatonia, amnesia, and analgesia, with or without actual loss of consciousness. The drug is an arylcyclohexylamine chemically related to phencyclidine (PCP), a drug frequently abused because of its psychoactive properties. The mechanism of action of ketamine may involve blockade of the... 

A review of the use of naloxone in mechanisms for the control of pain has been published395 and the effects of this compound on behaviour,254,396-415 the brain,284,416-419 various forms of shock,420-428 respiration,349 primary apnoea in neonates,429 the intake of food430-433 and of water,431 437 renal function,438 the gastro-intestinal tract,299,305 bodily temperature,439 memory,440 electroseizures,441 epilepsy,442 immuno-reactivity,325 ketamine narcosis,443 reserpine-induced... 

Marwaha, J. (1980a). Some mechanisms underlying actions of ketamine on electromechanical coupling in skeletal muscle. J. Neuro sci. Res. 5 43-50. 

The mechanism of PCP and ketamine action involves antagonism of a subset of receptors for the excitatory amino acid glutamate (Balazs et al., 2006). PCP is absorbed rapidly after smoking or injection, with peak blood concentrations noted 5-15 minutes after smoking. In contrast, peak concentrations are reached wo hours after oral administration. The drug remains in the system unmetabolized for more than nvo days, and PCP is detectable in urine for several weeks after a single use (Hawks Cliiang, 1986). 

Pathological bradyarrhythmias that affect cardiac output or peripheral perfusion require appropriate therapy. The primary aim of therapy should be the correction of the underlying disease mechanism electrolyte abnormalities should be corrected or the depth of anesthesia reduced as appropriate. An ct2 adrenoceptor antagonist (e.g. atipamezole) can be considered in animals sedated with the 02 adrenoceptor agonists but it should not be administered to animals anaesthetized with ketamine because of the risks of inducing ketamine-related excitement. Corticosteroids are indicated if myocardial inflammation is present. 

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