Excitatory

Steroid Hormones and Neurosteroids. Steroids (qv) can affect neuroendocrine function, stress responses, and behavioral sexual dimorphism (78,79) (see Steroids). Mineralocorticoid, glucocorticoid, androgen, estrogen, and progesterone receptors are localized in the brain and spinal cord. In addition to genomic actions, the neurosteroid can act more acutely to modulate the actions of other receptors or ion channels (80). Pregnenolone [145-13-17, ( ) dehydroepiandosterone [53-43-0] C H2 02 (319) are excitatory neurosteroids found in rat brain, independent of adrenal... 

SRIF acts as an excitatory neuromodulator in the CNS inhibiting the release of TRH, corticotropin-releasing hormone (CRH), growth hormone releasing factor (GHRH), and NE. It produces general arousal and hypotension. It inhibits the release of a number of peptides and modulators in the GI tract. 

AVP is excitatory in the ventral hippocampus, either directly or by potentiation of glutamatergic responses. An inhibitory effect has been observed in AVP may be involved in the formation of long-term potentiation and thus learning and memory. However, AVP is proconvulsive, may augment the formation of dmg tolerance and dependence, and affects cardiovascular regulatory processes. 

OT receptors in the hypothalamus are regulated by steroids. OT systems in the CNS are involved in homeostasis, reproduction, and related behavior. OT is also excitatory to neurons in the CNS at nanomolar concentrations (86), but relatively Httle is known about neuronal mechanisms and pharmacology. 

Fig. 14. The cellular ionic environment depicting representative intracellular ionic concentrations and the equiUbrium potentials, for individual ions. Excitatory and inhibitory events are represented by — and +, respectively. Thus, K" channel agonists and antagonists are inhibitory and excitatory, respectively Ca " channel antagonists and activators are inhibitory and excitatory, respectively.

Methohexital [18652-93-2] (Brevital), C 4H gN202, (2) is a barbiturate iv anesthetic iaduction agent that has a slightly faster onset than thiopentone and less accumulation. The recovery from anesthesia is also slightly faster and better. However, iaduction is associated with an iacreased iacidence of excitatory phenomena. Methohexital also causes respiratory and cardiovascular depression and is unstable ia solution, necessitating reconstitution before use (99). 

Propanidid. Propanidid [1421-14-3] (Epontol), C gH2yNO, (7) a derivative of the propyl ester of homo vanillic acid, has been in clinical use in Europe for a number of years. Its main advantage is rapid onset of action and a fast recovery which, like etomidate, is because of rapid metaboHsm by esterases rather than redistribution (108). Excretion is rapid 75 to 90% of the dmg is eliminated as metaboUtes within two hours. Propanidid side effects include hypotension, tachycardia, and hyperventilation followed by apnea, as well as excitatory side effects such as tremor and involuntary muscle movement (109). 

Compounds that have agonistic properties at glutamate or aspartate receptors are also CNS stimulants, readily cause convulsions, and presumably could also be employed as analeptics. Three separate excitatory amino acid receptor subtypes have been characterized pharmacologically, based on the relative potency of synthetic agonists. These three receptors are named for their respective prototypical agonists A/-methyl-D-aspartate [6384-92-5]... 

Excitability. Excitabihty refers to electrical responsiveness of the heart to various stimuli by the generation of local excitatory currents, action potentials, or fibrillation. 

Fig. 10.2 Schematic representation of connections in Rosenblatt s Photoreceptron [rosenbl58]. The synaptic connections from the S-units to A-units can be either excitatory or inhibitory connections between A-units and R-units may include inhibitory feedback loops. Response layer units are also linked to other R-units with inhibitory connections.

The distinction between a- and P-adrenergic receptors was first proposed by Ahlquist in 1948 based on experiments with various catecholamine derivatives to produce excitatory (a) or inhibitory (P) responses in isolated smooth muscle systems. Initially, a further subdivision into presynaptic a2- and postsynaptic oq-receptors was proposed. However, this anatomical classification of a-adrenergic recqrtor subtypes was later abandoned. 

Opioids G-protein coupled p-, 5-, k-receptors l cAMP l Ca2+ currents t K+ currents l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters p, 5 sedation, nausea, euphoria/re-ward, respiratory depression, constipation k dysphoria/aversion, diuresis, sedation... 

Serotonin agonists G-protein coupled 5-HT receptors 5-HT3 ion channels cAMP (5-HT-,) t cAMP (5-HT4 7) t PLC (5-HT2) l Release of excitatory neuropeptides l Neurogenic inflammation f vasoconstriction Myocardial infarction, stroke, peripheral vascular occlusion... 

Altered synaptic properties Numerous changes in the properties of inhibitory (GABAergic) and excitatory (glutamatergic) synapses have been reported. While the simple adage of an imbalance between inhibitory and excitatory neurotransmission in epilepsy is not generally applicable, some forms of inhibition are lost or impaired in epilepsy. Likewise, an increased function of glutamate receptors has been demonstrated in some brain areas. 

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