**1. Introduction**

In the world, about 1% of people suffer from epilepsy [1]. Modern anticonvulsants can prevent and decrease the intensity of these convulsions. However, about 30% of people with epilepsy have uncontrollable seizures although of drugs availability. It is also known that the therapy ineffectiveness and chronic toxicity of antiepileptic drugs drawbacks the treatment procedure for nearly 20% of the patients [2].

Tobacco smoke is a complex multicomponent system, in which more than 4800 compounds, many of which are known carcinogens. As a result, chronic obstructive pulmonary disease, chronic bronchitis, cardiovascular disease, emphysema, stroke and many forms of cancer are directly related to smoking [3].

In March 2012, the Food and Drug Administration established a long list containing 93 harmful and potentially harmful components (HPHCs) and an abbreviated list containing 18 HPHCs in tobacco products and tobacco smoke (**Table 1**).

However, seizure control in the majority of epileptic patients is achieved primarily through the pharmacotherapeutic action of drugs targeting membrane ion channels or glutamatergic or gabaergic neurotransmission [4], which is dependent on a wide variety of modifications., glutamate and GABA [5]. For example, a weak activation of the GABAergic system induces epilepsy [6]. Generally, the risk of epilepsy should be higher in chronic tobacco smokers; this behavior is due to toxic components of tobacco smoke that can lead to seizure behavior in humans and animals [7, 8].

Many components in tobacco smoke are associated with seizures or epilepsy (**Table 2**) [9]. For example, nicotine, when overdosed, caused seizures in human subjects. Nicotine, a parasympathomimetic alkaloid in tobacco when overdosed, caused seizures in human [10]. The carbon monoxide causes seizures that can be focal or generalized and may even present as a status of epilepticus [11, 12]. Ammonia, hexane, lead, cresol, arsenic, toluene and acetone are other chemicals found in tobacco smoke that can trigger seizures in humans or animals [13].


*See Ref. [4].\* 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone.*

*\*\*N-Nitrosonornicotine.*

*a Roll-your-own tobacco is defined in section 900(15) of the FD&C Act to mean "any tobacco product which, because of its appearance, type, packaging, or labeling, is suitable for use and likely to be offered to, or purchased by, consumers as tobacco for making cigarettes." The term cigarette filler is not defined in the FD&C Act. For purposes of this draft guidance, we intend cigarette filler to mean the cut, ground, powdered, or leaf tobacco that is a component of a cigarette.*

**35**

*Cerebroventricular Injection of Cigarette Smoke Condensate Produce Generalized Seizures…*

**Seizure-inducing Potentiating seizures**

5% carbon dioxide Low dose increased the severity of the electroshock-

Toluene clonus (M) Increased susceptibility to aminophylline-induced

induced seizures (M)

seizures (IP) (M)

Potentiated PTZ-induced convulsions (M)

Animals have been a useful tool for elucidating the association between tobacco smoking or nicotine use and seizures or epilepsy. Nicotine induced seizure models include cats, mice, and rats, and it was reported that animals received nicotine via injection develop seizures but not through the automatic smoking machine (ASM) [14, 15]. Other studies have shown that the activity of seizure-inducing chemicals such as pentylenetetrazole [16], kainic acid, pilocarpine, had been enhanced by

In this study, we have investigated the convulsive effect of CSC as a crisis model compared to the intensity of the kainic acid model of epilepsy in rats. Thus examine the role of the cholinergic system in cigarette condensate seizures using a treatment

**2. Epileptic behavior induced by cerebral injection of cigarette smoke** 

The objective of the experiment was to demonstrate that a treatment with cigarette smoke condensate provides an epileptic behavior similar to this induced by

The preparation of the cigarette smoke condensate was carried out by a cooling system consisting of a VP800 vacuum pump that generates and removes cigarette smoke to a tube and a balloon where the cigarette condensate is recovered [13]. Male

a kainic acid, who reduced by a pretreatment with atropine.

*DOI: http://dx.doi.org/10.5772/intechopen.85402*

Nicotine Nicotine patch (H)a

Lead acetate High dose induced

Acetone High dose caused

forelimb

seizures (M)

*Effects of chemicals in tobacco smoke on seizures or epilepsy.*

Carbon monoxide (H)

Ammonia (H), (R) Hexane (H)

Cresol (H)

*H: human; M: mouse; R: rat.*

**Chemicals in tobacco smoke**

Arsenic

Selenium Zinc Copper Nickel

*a*

**Table 2.**

prior pretreatment with nicotine [17].

with cholinergic muscarinic ligand.

**condensate**

**2.1 Methodology**

### **Table 1.**

*Abbreviated list of harmful and potentially harmful constituents (HPHCs) in tobacco products.*

*Cerebroventricular Injection of Cigarette Smoke Condensate Produce Generalized Seizures… DOI: http://dx.doi.org/10.5772/intechopen.85402*


### **Table 2.**

*Epilepsy - Advances in Diagnosis and Therapy*

**HPHCs in cigarette smoke HPHCs in smokeless** 

Ammonia Nicotine (total and free)

Benzene NNK*\** Benzo[a]pyrene NNN\*\*

1,3-Butadiene Carbon monoxide Crotonaldehyde Formaldehyde Isoprene Nicotine (total)

NNK\* NNN\*\* Toluene *See Ref. [4].\**

*\*\*N-Nitrosonornicotine.*

**tobacco**

1-Aminonaphthalene Crotonaldehyde NNK\* 2-Aminonaphthalene Formaldehyde NNN*\*\**

*4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone.*

*Roll-your-own tobacco is defined in section 900(15) of the FD&C Act to mean "any tobacco product which, because of its appearance, type, packaging, or labeling, is suitable for use and likely to be offered to, or purchased by, consumers as tobacco for making cigarettes." The term cigarette filler is not defined in the FD&C Act. For purposes of this draft guidance, we intend cigarette filler to mean the cut, ground, powdered, or leaf tobacco that is a component of a* 

*Abbreviated list of harmful and potentially harmful constituents (HPHCs) in tobacco products.*

Acetaldehyde Acetaldehyde Ammonia Acrolein Arsenic Arsenic Acrylonitrile Benzo[a]pyrene Cadmium 4-Aminobiphenyl Cadmium Nicotine (total)

animals [7, 8].

In March 2012, the Food and Drug Administration established a long list containing 93 harmful and potentially harmful components (HPHCs) and an abbreviated list containing 18 HPHCs in tobacco products and tobacco smoke (**Table 1**). However, seizure control in the majority of epileptic patients is achieved primarily through the pharmacotherapeutic action of drugs targeting membrane ion channels or glutamatergic or gabaergic neurotransmission [4], which is dependent on a wide variety of modifications., glutamate and GABA [5]. For example, a weak activation of the GABAergic system induces epilepsy [6]. Generally, the risk of epilepsy should be higher in chronic tobacco smokers; this behavior is due to toxic components of tobacco smoke that can lead to seizure behavior in humans and

Many components in tobacco smoke are associated with seizures or epilepsy (**Table 2**) [9]. For example, nicotine, when overdosed, caused seizures in human subjects. Nicotine, a parasympathomimetic alkaloid in tobacco when overdosed, caused seizures in human [10]. The carbon monoxide causes seizures that can be focal or generalized and may even present as a status of epilepticus [11, 12]. Ammonia, hexane, lead, cresol, arsenic, toluene and acetone are other chemicals found in tobacco smoke that can trigger seizures in humans or animals [13].

**HPHCs in roll-your-own tobaccoa**

**cigarette filler**

 **and** 

**34**

*a*

*cigarette.*

**Table 1.**

*Effects of chemicals in tobacco smoke on seizures or epilepsy.*

Animals have been a useful tool for elucidating the association between tobacco smoking or nicotine use and seizures or epilepsy. Nicotine induced seizure models include cats, mice, and rats, and it was reported that animals received nicotine via injection develop seizures but not through the automatic smoking machine (ASM) [14, 15]. Other studies have shown that the activity of seizure-inducing chemicals such as pentylenetetrazole [16], kainic acid, pilocarpine, had been enhanced by prior pretreatment with nicotine [17].

In this study, we have investigated the convulsive effect of CSC as a crisis model compared to the intensity of the kainic acid model of epilepsy in rats. Thus examine the role of the cholinergic system in cigarette condensate seizures using a treatment with cholinergic muscarinic ligand.
